Reactions of simple aromatic heterocycles with niobium cluster ions (n < or = 30).
Prior work on benzene activation by size selected niobium cluster cations and anions of up to 30 atoms is extended systematically through studying aromatic poly- and heterocyclic molecules such as naphthalene, pyridine, thiophene, pyrrole, furan, and benzofuran. Naphthalene is found to act much like benzene when reacting under single collision conditions with individual clusters. The most likely process is carbidization through complete dehydrogenation. Some clusters of particular sizes (most notably n=19) fail to activate both homocyclic molecules. Instead seemingly intact adsorption is observed which proves that activation is kinetically hindered at some point. All of the five studied heterocyclic aromatic molecules react unconditionally and by complete dehydrogenation with cationic niobium clusters, while they only attach to or react with anionic clusters larger than a minimum size of n=19-21. These findings are taken as strong evidence for initial coordination to the metal clusters of the heterocycles through their lone pair orbitals. The paper comprehends the observations in terms of cluster surface structure and reactivity.


Adrenal sarcomatoid carcinoma: a rare case depicted on multi-detector row computed tomography.
Primary adrenal sarcomatoid carcinoma is rare malignant tumor with the characteristics of carcinoma and sarcoma. To date, only one case of primary sarcomatoid carcinoma in the adrenal gland was reported. We present here computed tomography appearance and pathological features of the case with primary adrenal sarcomatoid carcinoma confirmed by pathology. In addition, a brief review of the relevant literature is presented.


The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma.
The cysteinyl-leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti-leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma. Solid-phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum-specific IgE and severity of allergy and asthma were examined. Family-based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper-responsiveness to methacholine or forced expiratory volume in 1 s. Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.


Effect of ligand groups on photoexcited charge carrier dynamics at the perovskite/TiO2 interface.
The work proposed here aims to describe the dynamics of photoexcited charge carriers at the interface between the perovskite and electron transport layer (ETL) in perovskite solar cells (PSCs) and the effect that the interface morphology has on these dynamics. This is done in an effort to further develop the understanding of these materials so that their chemical composition and morphology may be better utilized to improve PSCs by means of increasing the power conversion efficiency (PCE), maximizing the chemical stability of PSCs to lengthen their lifespan, finding the cheapest and easiest materials to synthesize which have beneficial properties in photovoltaics, etc. This is done by using density functional theory to model the interface and open system Redfield theory to describe the charge carrier dynamics. We find that the charge transfer characteristics at the perovskite/ETL interface depend greatly on the choice of ligands adsorbed on the ETL that act as a bridge between the perovskite and ETL. The two ligand choices discussed here go so far as to determine whether the system will undergo a Förster energy transfer or a Dexter energy transfer upon photoexcitation.


Use of the Microheterogeneous Model to Assess the Applicability of Ion-Exchange Membranes in the Process of Generating Electricity from a Concentration Gradient.
The paper shows the possibility of using a microheterogeneous model to estimate the transport numbers of counterions through ion-exchange membranes. It is possible to calculate the open-circuit potential and power density of the reverse electrodialyzer using the data obtained. Eight samples of heterogeneous ion-exchange membranes were studied, two samples for each of the following types of membranes: Ralex CM, Ralex AMH, MK-40, and MA-41. Samples in each pair differed in the year of production and storage conditions. In the work, these samples were named "batch 1" and "batch 2". According to the microheterogeneous model, to calculate the transport numbers of counterions, it is necessary to use the concentration dependence of the electrical conductivity and diffusion permeability. The electrolyte used was a sodium chloride solution with a concentration range corresponding to the conditional composition of river water and the salinity of the Black Sea. During the research, it was found that samples of Ralex membranes of different batches have similar characteristics over the entire range of investigated concentrations. The calculated values of the transfer numbers for membranes of different batches differ insignificantly: ±0.01 for Ralex AMH in 1 M NaCl. For MK-40 and MA-41 membranes, a significant scatter of characteristics was found, especially in concentrated solutions. As a result, in 1 M NaCl, the transport numbers differ by ±0.05 for MK-40 and ±0.1 for MA-41. The value of the open circuit potential for the Ralex membrane pair showed that the experimental values of the potential are slightly lower than the theoretical ones. At the same time, the maximum calculated power density is higher than the experimental values. The maximum power density achieved in the experiment on reverse electrodialysis was 0.22 W/m2, which is in good agreement with the known literature data for heterogeneous membranes. The discrepancy between the experimental and theoretical data may be the difference in the characteristics of the membranes used in the reverse electrodialysis process from the tested samples and does not consider the shadow effect of the spacer in the channels of the electrodialyzer.


Preoperative planning and postoperative imaging in shoulder arthroplasty.
The number of shoulder arthroplasties performed in the United States has more than doubled in the last decade. Additionally, there has been a trend toward use of reverse total shoulder arthroplasty and minimally invasive surgical techniques, such as resurfacing humeral head arthroplasty. Thus radiologists will more frequently encounter imaging of shoulder arthroplasty and these new designs. Successful postoperative radiologic evaluation of shoulder reconstructions requires an understanding of their fundamental hardware design, physiologic objective, preoperative imaging assessment, normal postoperative radiologic appearance, and findings and types of complication. This article discusses the designs of prostheses used around the shoulder joint, delineates indications and alternatives for each of the different types of hardware, reviews radiographic and cross-sectional preoperative imaging of shoulder arthroplasty, illustrates normal postoperative imaging findings and measurements, and provides examples of hardware complications.


Effect of ovariectomy and estrogen supplementation on brain acetylcholinesterase activity and passive-avoidance learning in rats.
The effect of ovariectomy and estrogen treatment on the brain acetylcholinesterase activity and cognition in rats was investigated in this study. Ovariectomized and nonovariectomized rats were treated subcutaneously with estradiol dipropionate for 8 d. In the single-trial, passive-avoidance test all the groups showed significant learning and retention of memory as evident by the increase in transfer latency time in trial 2 as compared with trial 1. No-transfer response was significantly increased in the estradiol-dipropionate-treated ovariectomized (80%) and nonovariectomized (60%) group as compared with the ovariectomized (30%) group. Specific activity of acetylcholinesterase was assayed spectrophotometrically in salt-soluble and detergent-soluble fractions of various brain areas: frontal cortex, cerebral cortex, striatum, hippocampus and hypothalamus, thalamus, pons, medulla, and cerebellum. The effect of ovariectomy and estradiol dipropionate was varied in both fractions of these brain areas. Estradiol dipropionate treatment could restore the acetylcholinesterase activity to the control level only in the detergent-soluble fraction of hypothalamus and salt-soluble fraction of hypothalamus, thalamus, and medulla in ovariectomized rats. The results indicate that ovariectomy alters acetylcholinesterase activity in the brain areas but not in a uniform manner and affects only qualitative aspects of cognitive function, which could be improved by estrogen supplementation.


Occupational allergic rhinitis reaction to psyllium.
We report studies that document a specific rhinitic reaction that developed as a result of occupational exposure to a psyllium-based powdered laxative. This nurse had a nonatopic family history, personal evidence of atopy (skin test reactions to pollen, cat dander, and house dust), and a significant elevation of antipsyllium IgE. Measurements of nasal and lower airway resistance documented only nasal obstruction to brief inhalational challenge to the laxative. Symptomatic relief was achieved with prior treatment with cromolyn. We suggest that nasal airway challenge can document and assess treatment for occupational rhinitis.


Morphological Eyelids Changing After Orthognathic Surgery in Long-Face Syndrome.
The aim of the authors study is to demonstrate the soft tissues changes in the eyelid-brow area (ELBA) in patients with long-face syndrome after LeFort I osteotomy and impaction movements. To perform this study the authors have analyzed retrospectively orthognathic patients with at least 1 years of completely follow-up. The inclusion criteria were: long-face syndrome according to Farkas' studies and vertical maxillary shortening movement without considering whether movements have been made in the other 2 planes of space (sagittal and horizontal).Orthognathic patients in which the maxillary impaction movement did not correlate to the long-face syndrome represented the control group. In this group too the authors did not consider if other movements were performed.Size and shape of the eyelid and the eyebrow was assessed on the frontal patients photos calibrated on the three-dimensional soft tissue volume imported from cone beam computed tomography.Two reference lines were taken: a horizontal line from the nasal point passing through both medial canthal angles and a perpendicular line through the pupil centre bilaterally. Then the measures were taken.The same operator (A.C.) took all of the measurements.In both groups, the preoperative measures were then compared with the postoperative ones. Then the soft tissue changes in both groups were compared. The results demonstrate different reaction of the ELBA after orthognathic surgery. The ELBA's position changes in long-face patients in a higher position after maxillary impaction. The authors did not obtain the same results in patients who do not have long-face syndrome. Repositioning skeletal bases in patients with long face causes a change in the ELBA's morphology.


Viscoelastic and chemical properties of dentine after different exposure times to sodium hypochlorite, ethylenediaminetetraacetic acid and calcium hydroxide.
This study aims to evaluate the viscoelastic and chemical properties of dentine after different durations of exposure to 5.25% NaOCl, 17% EDTA and Ca(OH)2 solutions, and NaOCl in alternating combination with EDTA. Standard dentine bars were randomly assigned to: (i) formal-saline control-1; (ii) NaOCl; (iii) EDTA; (iv) NaOCl/EDTA; (v) formal-saline control-2; (vi) Ca(OH)2 pH 12.6; and (vii) Ca(OH)2 pH 9.8. Groups 1--4 underwent 10 min cycles of soaking and dynamic mechanical analysis up to 120 min. Groups 5-7 underwent similar tests at days 7, 14, 28 and 84. FTIR spectra of dentine discs exposed to the same regimens assessed surface chemistry. NaOCl or Ca(OH)2 (pH 12.6) solutions reduced the organic (N-H[1], N-H[3], C=0) peak components of dentine. This study demonstrated that accumulative damage of dentine could be facilitated by alternated exposure to NaOCl and EDTA. Exposure of dentine to Ca(OH)2 (pH12.6) for 7 days reduced viscous behaviour, inferring increased potential for fatigue failure.


Comparison of minimum inhibitory concentration values determined by three antimicrobic dilution methods for Pseudomonas aeruginosa.
This investigation compares minimum inhibitory concentration measurements by three antimicrobic dilution methods for Pseudomonas aeruginosa versus seven antimicrobics. Minimum inhibitory concentrations were measured for 650 P. aeruginosa clinical isolates and for repeated tests with P. aeruginosa ATCC 27853 versus gentamicin, tobramycin, amikacin, netilmicin, sisomicin, carbenicillin, and ticarcillin, using the macro-broth, micro-broth, and agar dilution methods. For all antimicrobics, it was found that the micro-broth and agar dilution methods produced comparable minimum inhibitory concentration measurements, which were found to lie 1 to 2 double dilution steps below those determined by the macro-broth method. Acceptably replicability was found for both the macro-broth and the agar dilution methods. The micro-broth method showed less replicability, with 4.7% of minimum inhibitory concentration values lying +/- 2 or more double dilution steps from the modal value. It is important to recognize such differences if micro-broth or agar dilution methods are substituted for the macro-broth method.


Advances in the application of proteomics in lung cancer.
Although the incidence and mortality of lung cancer have decreased significantly in the past decade, it is still one of the leading causes of death, which greatly impairs people's life and health. Proteomics is an emerging technology that involves the application of techniques for identifying and quantifying the overall proteins in cells, tissues and organisms, and can be combined with genomics, transcriptomics to form a multi-omics research model. By comparing the content of proteins between normal and tumor tissues, proteomics can be applied to different clinical aspects like diagnosis, treatment, and prognosis, especially the exploration of disease biomarkers and therapeutic targets. The applications of proteomics have promoted the research on lung cancer. To figure out potential applications of proteomics associated with lung cancer, we summarized the role of proteomics in studies about tumorigenesis, diagnosis, prognosis, treatment and resistance of lung cancer in this review, which will provide guidance for more rational application of proteomics and potential therapeutic strategies of lung cancer.


Congenital fibrous epulis in the infant.
Congenital fibrous epulis is an extremely rare tumor of infancy. It is a benign gingival tumor and generally seen in maxillary alveolar crest and its etiology remains the subject of debate. Congenital fibrous epulis could be considered a hamartomatous lesion. Histologically it does not show the closely packed large granular cells necessary for the diagnosis of an ordinary congenital epulis. Instead, it consists of irregular bundles of collagenous connective tissue, varying numbers of fusiform cells with oval or fusiform shaped nuclei and mild subepithelial inflammatory infiltration with tiny blood vessels and in this case a woven bone spicule in the deep area. Recommended treatment for this tumor is simple excision. We report upon a case of congenital fibrous epulis in a male infant and discuss the clinical features, histopathologic findings, and surgical treatment.


A study of tinea capitis in Sri Lanka.
Between January 1978 and December 1987, 106 cases of tinea capitis were detected in Sri Lanka. Diagnosis was confirmed mycologically by microscopic examination and by culture. Tinea capitis accounted for 3.4% of all superficial fungal infections seen during this period. This figure is low when compared with the incidence of this disease reported in other countries. Five main types of clinical manifestation were encountered. Inflammatory lesions were observed in 50% of the patients. Eighty-five percent of infections occurred in children below 15 years of age and 76% in children under 10 years of age. The 6-10 year age group was the most vulnerable. The zoophilic fungi Trichophyton mentagrophytes, Microsporum canis and the geophilic species Microsporum gypseum were together responsible for 81% of tinea capitis infections, and the zoophilic fungus Trichophyton simii accounted for a further 10% of infections. It is postulated that the Sri Lankan custom of frequent head baths with soap and water, especially among children, may account in part for the low prevalence of tinea capitis in the community.


Velocity bias in intrusive gas-liquid flow measurements.
Gas-liquid flows occur in many natural environments such as breaking waves, river rapids and human-made systems, including nuclear reactors and water treatment or conveyance infrastructure. Such two-phase flows are commonly investigated using phase-detection intrusive probes, yielding velocities that are considered to be directly representative of bubble velocities. Using different state-of-the-art instruments and analysis algorithms, we show that bubble-probe interactions lead to an underestimation of the real bubble velocity due to surface tension. To overcome this velocity bias, a correction method is formulated based on a force balance on the bubble. The proposed methodology allows to assess the bubble-probe interaction bias for various types of gas-liquid flows and to recover the undisturbed real bubble velocity. We show that the velocity bias is strong in laboratory scale investigations and therefore may affect the extrapolation of results to full scale. The correction method increases the accuracy of bubble velocity estimations, thereby enabling a deeper understanding of fundamental gas-liquid flow processes.


Identification of a Strigoterpenoid with Dual Nrf2 and Nf-κB Modulatory Activity.
The sesquiterpene-coumarin ether samarcandone provided a suitable framework to replace the apocarotenoid A-C ring system of strigol (1), replicating, after linking to a butenolide moiety, the activity of the natural phytohormone on Nrf2 and also showing potent NF-kB inhibitory activity, overall modulating two critical pathways of inflammation and cancer.


[Mechanisms involved in the regulation of immune response in animal model of rheumatoid arthritis in mice (CIA)].
Rheumatoid arthritis (RA) represents an example of the autoimmune disease. With a prevalence of 1% worldwide, the pathogenesis of RA is not clear yet. At present it is thought that the pathogenesis of RA results from an inflammatory response mediated by CD4+ Th1 cells that recognize unidentified antigens present in bone joints. Recently, there is a growing evidence for a role for Th17 lymphocytes in autoimmunity, including RA, suggesting that this population of helper cells may be more important in the pathogenesis of RA than Th1 cells. Thus far, treatment modalities for RA are limited, with the prevailing one acting nonspecifically on the immune system. However, such an approach results in a general immunosuppression and is accompanied by severe side-effects. There is a large demand for developing RA therapy that particularly targets pathogenic antigen-specific T cells. Research on pathogenesis of the autoimmune diseases, and development of new drugs is now possible thanks to experimental animal models that mimic human diseases. Collagen-induced arthritis (CIA) in genetically susceptible strains of mice, rats, rabbits or rhesus monkeys has been used as an experimental model of RA, as it shares many histological and immunological features. The knowledge gained using this model allows to better understand the pathogenesis of RA and, consequently, to manipulate particular components of the immune system to develop efficient therapies.


The complete mitochondrial genome of the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).
The complete mitochondrial genome (mitogenome) of Plutella xylostella (Lepidoptera: Plutellidae) was determined (GenBank accession No. KM023645). The length of this mitogenome is 16,014 bp with 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and an A + T-rich region. It presents the typical gene organization and order for completely sequenced lepidopteran mitogenomes. The nucleotide composition of the genome is highly A + T biased, accounting for 81.48%, with a slightly positive AT skewness (0.005). All PCGs are initiated by typical ATN codons, except for the gene cox1, which uses CGA as its start codon. Some PCGs harbor TA (nad5) or incomplete termination codon T (cox1, cox2, nad2 and nad4), while others use TAA as their termination codons. The A + T-rich region is located between rrnS and trnM with a length of 888 bp.


Palatability and digestibility of soya- and milk proteins in Callithricidae.
4 protein sources were tested for palatability, digestibility, influence on bodyweight and consistency of faeces in Callithrix jacchus and Saguinus fuscicollis. The protein sources were incorporated at crude protein levels of 12, 17 and 22% in a pelleted diet. A banana supplement was also fed which reduced the total protein content to 10.7, 14.7 and 18.3%. The test diets, fed for 3 weeks, were well accepted with the milk proteins being slightly preferred. Consumption of the 12% protein pellets was greater than their 22% equivalents. True protein digestibility was calculated to be 97% for lactalbumin, 96% for casein, 90% for soy protein concentrate and 83% for soyabean meal. Changes in bodyweight were negligible. Dry matter of faeces varied between 25% (lactalbumin diets) and 28% (casein diets), but did not change with increasing protein intake. Increasing levels of cellulose, from 2.4 to 7.2% total crude fibre lowered the apparent protein digestibility from 84.3 to 79.2% and the digestibility of dry matter from 82.2 to 76.5%.


Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Melbourne Diabetic Nephropathy Study Group.
To compare the efficacy of angiotensin converting enzyme inhibition with calcium antagonism in diabetic patients with microalbuminuria. Randomised study of diabetic patients with microalbuminuria treated with perindopril or nifedipine for 12 months and monitored for one or three months after stopping treatment depending on whether they were hypertensive or normotensive. Patients were randomised separately according to whether they were hypertensive or normotensive. Diabetic clinics in three university teaching hospitals. 50 diabetic patients with persistent microalbuminuria. In all, 43 completed the study: 30 were normotensive and 13 hypertensive; 19 had type I diabetes and 24 had type II diabetes. For 12 months 20 patients were given perindopril 2-8 mg daily and 23 were given nifedipine 20-80 mg daily. Albumin excretion rate, blood pressure, and glomerular filtration rate. Both perindopril and nifedipine significantly reduced mean blood pressure. During treatment there was no significant difference between those treated with perindopril and those treated with nifedipine with respect to albuminuria or mean blood pressure. Stopping treatment with both drugs was associated with a sustained increase in albuminuria and mean blood pressure. There was a significant correlation between mean blood pressure and albuminuria and also between the reduction in mean blood pressure and the decrease in albuminuria during treatment with both drugs. In hypertensive patients both drugs caused significant decreases in mean blood pressure and albuminuria. In normotensive patients there was no significant reduction in albuminuria with either regimen. In diabetic patients with microalbuminuria blood pressure seems to be an important determinant of urinary albumin excretion. Perindopril and nifedipine have similar effects on urinary albumin excretion, both preventing increases in albuminuria in normotensive patients and decreasing albuminuria in hypertensive patients.


Interaction of fluorescently substituted metallacarboranes with cyclodextrins and phospholipid bilayers: fluorescence and light scattering study.
We prepared two fluorescein-[3-cobalt(III) bis(1,2-dicarbollide)](-) conjugates. They are sparingly soluble in water and form large aggregates in aqueous solutions. An extensive study on their spectral and aggregation behavior was carried out. To prepare their well-defined dispersion in aqueous systems, we studied the interaction of both probes with two biocompatible amphiphilic systems, cyclodextrins, which are frequently used in drug-delivery systems, and phospholipid membranes, which are the major constituents of cell barriers in living organisms. The presence of fluorescein in both conjugates allows us to study their behavior in detail by steady-state and time-resolved fluorometry, fluorescence correlation spectroscopy, and fluorescence lifetime imaging. The self-assembly of these metallacarboranes in aqueous solutions was studied by dynamic light scattering. The study shows that the compounds interact with cyclodextrins that increases their solubility in water, and they solubilize easily in phospholipid bilayers.


Signals use by leaders in Macaca tonkeana and Macaca mulatta: group-mate recruitment and behaviour monitoring.
Animals living in groups have to make consensus decisions and communicate with each other about the time, or the direction, in which to move. In some species, the process relies on the proposition of a single individual, i.e. a first individual suggests a movement and the other group members decide whether or not to join this individual. In Tonkean (Macaca tonkeana) and rhesus macaques (Macaca mulatta), it has been observed that this first individual displays specific signals at departure. In this paper, we aimed to explore the function of such behaviours, i.e. if these behaviours were recruitment signals or only cues about the motivation of the first departed individual. We carried out temporal analyses and studied the latencies of the first departed individual's behaviours and of the joining of other group members. We also assessed whether the social style of a species in terms of dominance and kinship relationships influenced the patterns of signal emissions. We then analyzed how the first departed individual decided to make a pause or to stop it according to the identities of group members that joined the collective movement. Results showed that Tonkean macaques and rhesus macaques seemed to use back-glances to monitor the joining of other group members and pauses to recruit such individuals. This was especially the case for highly socially affiliated individuals in Tonkean macaques and kin-related individuals in rhesus macaques. Moreover, back-glances and pauses disappeared when such individuals joined the first departed individual. From these results, we suggested that such behaviour could be considered intentional. Such findings could not be highlighted without temporal analyses and accurate observations on primate groups in semi-free ranging conditions.


Density dependent regulation of human Schwann cell proliferation.
Cessation of division is prerequisite for Schwann cell differentiation but regulation of this critical function is poorly understood. Heregulin/forskolin-induced growth of human Schwann cells (HSCs) in vitro was found to be strongly regulated by cell density and thus could model some aspects of negative growth-regulation in vivo. To better understand this phenomenon, the production of an autocrine growth-inhibitor and the role of contact-inhibition were investigated. The possible involvement of two membrane proteins, contactinhibin (CI) and peripheral myelin protein 22 (PMP22) in regulating growth was studied. Thymidine-labeling of HSCs on collagen-coated dishes was inhibited at cell densities less than one tenth of the density at maximal growth-inhibition. Medium from high density cultures did not inhibit the thymidine-labeling of HSCs at low density, a result that argues against the production of a soluble inhibitor. The expression of CI and PMP22 in nerve and HSCs, and the effect of a function-blocking antibody to CI on HSC growth, were determined. CI was detected in fresh nerve by western blotting, and could easily be detected by immunocytochemistry in cultured HSCs by five days and for several weeks thereafter. Twenty-four hour treatment with anti-CI antibody did not increase the thymidine-labeling of HSCs at any density but a significant increase in HSC number was observed in cultures treated with anti-CI for 20 days. This increase was not related to decreased cell death. PMP22, unlike other myelin proteins, was not down-regulated after nerve dissociation and by seven days nearly all HSCs were PMP22 positive. These results provide evidence for a contact-mediated mechanism of growth-regulation in HSCs and suggest that CI is involved in this mechanism.


Olfaction in neurologic and neurodegenerative diseases: a literature review.
Introduction Loss of smell is involved in various neurologic and neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. However, the olfactory test is usually neglected by physicians at large. Objective The aim of this study was to review the current literature about the relationship between olfactory dysfunction and neurologic and neurodegenerative diseases. Data Synthesis Twenty-seven studies were selected for analysis, and the olfactory system, olfaction, and the association between the olfactory dysfunction and dementias were reviewed. Furthermore, is described an up to date in olfaction. Conclusion Otolaryngologist should remember the importance of olfaction evaluation in daily practice. Furthermore, neurologists and physicians in general should include olfactory tests in the screening of those at higher risk of dementia.


Skip lymph node metastasis in gastric cancer: is it skipping or skipped?
Skip metastasis is the presence of a metastatic lymph node (LN) in an extraperigastric (EP) area without perigastric (PG) involvement. The mechanism and prognosis of skip metastasis are still unknown. The purpose of this study was to scrutinize the clinical significance of skip metastasis in gastric cancer. Data were reviewed from 6,025 patients who had undergone gastrectomy for primary gastric cancer. Patients were categorized as a PG-only group when the metastatic LNs were limited to only the PG area, as a PG + EP group if metastatic LNs extended to both the PG area and the EP area, and as a skip group if metastatic LNs were in the EP area but there were no metastatic LNs in the PG area. After we had performed matching, the prognosis of the skip group was worse than that of the PG-only group (adjusted hazard ratio 1.69, 95% confidence interval 1.13-2.54) and was similar to that of the PG + EP group (adjusted hazard ratio: 1.54, 95% confidence interval 0.92-2.59). The number of retrieved LNs was less in the skip group than in the other groups, especially from the PG area (p < 0.001). The prognosis of the skip group was worse than that of the PG-only group and was similar to that of the PG + EP group when the tumor stage was considered. It is difficult to conclude whether skip metastasis is real skipping of cancer cells or a result of inadequate LN sampling. Further evaluation of LNs in the PG area of the skip group could provide more clues for the mechanism of skip metastasis.


The diagnostic value of circulating abnormal cells in early lung cancer.
Lung cancer is the leading cause of cancer-related deaths globally. Early detection of lung cancer can lead to more effective treatment and improved survival. Circulatory abnormal cells (CACs) with specific chromosomal variation may be used to diagnose lung cancer and to differentiate benign from malignant nodules. The value of CAC in precancer diagnosis, however, remains controversial. In this study, a systematic review and meta-analysis are conducted to clarify the diagnostic value of CAC in early-stage lung cancer. A systematic literature search was conducted using the following medical topic title terms and text-free words: "circulating genetically abnormal cells", "CACs", "liquid biopsy", "early lung cancer", "non-small cell lung cancer", "diagnostic accuracy", "sensitivity" and "specificity" in Science Direct, CNKI and Wanfang databases, respectively. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were analyzed by STATA15.0 (MP) software. Deek funnel plots were used to assess potential publication bias. Heterogeneity was tested using the I2 statistic and the Cochrane Q test. 7 major studies were included in this meta-analysis, and a total of 53728 participants were analyzed. In the diagnosis of early lung cancer, CAC had pooled sensitivity, specificity, and receiver operating characteristics of 0.80 (95% CI: 0.73-0.86), 0.85 (95% CI: 0.69-0.94), and 0.87 (95% CI: 0.84-0.90). The combined positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and diagnostic score were 23.36 (95% CI: 7.33-74.46), 5.42 (95% CI: 2.37-12.43), 0.23 (95% CI: 0.16-0.35) and 3.15 (95% CI: 1.99-4.31) respectively. Publication bias was not detected. The CAC is effective at detecting lung cancer in its early stages.


Bacteriophage-Host Association in the Phytoplasma Insect Vector Euscelidius variegatus.
Insect vectors transmit viruses and bacteria that can cause severe diseases in plants and economic losses due to a decrease in crop production. Insect vectors, like all other organisms, are colonized by a community of various microorganisms, which can influence their physiology, ecology, evolution, and also their competence as vectors. The important ecological meaning of bacteriophages in various ecosystems and their role in microbial communities has emerged in the past decade. However, only a few phages have been described so far in insect microbiomes. The leafhopper Euscelidius variegatus is a laboratory vector of the phytoplasma causing Flavescence dorée, a severe grapevine disease that threatens viticulture in Europe. Here, the presence of a temperate bacteriophage in E. variegatus (named Euscelidius variegatus phage 1, EVP-1) was revealed through both insect transcriptome analyses and electron microscopic observations. The bacterial host was isolated in axenic culture and identified as the bacterial endosymbiont of E. variegatus (BEV), recently assigned to the genus Candidatus Symbiopectobacterium. BEV harbors multiple prophages that become active in culture, suggesting that different environments can trigger different mechanisms, finely regulating the interactions among phages. Understanding the complex relationships within insect vector microbiomes may help in revealing possible microbe influences on pathogen transmission, and it is a crucial step toward innovative sustainable strategies for disease management in agriculture.


[Differential therapy of infectious diarrhea].
Worldwide, diarrheal diseases caused by communicable pathogens rank first in morbidity and mortality, particularly in young children. Underprivileged groups of poor societies may still suffer from endemic typhus, bacillary dysentery, or cholera. In children however, a significant proportion of recurrent diarrhoeal episodes is caused by toxigenic enterobacteria, non-thyphoidal salmonella, campylobacter, and viruses. Although outbreaks of classical waterborne epidemics have not been reported from industrialized nations, infectious diarrhea is by no means scarce. Industrial cattlebreeding and food production facilitate the spread of nonthyphoidal salmonella, Campylobacter, and possibly Yersinia enterocolitica. Changes in travel patterns, an increasing number of immunocompromised patients, and migration of people from countries with lower sanitary standards warrants awareness to hitherto exceptional pathogens.


Antibiotic heliomycin and its water-soluble 4-aminomethylated derivative provoke cell death in T24 bladder cancer cells by targeting sirtuin 1 (SIRT1).
Bladder cancer is one of the most frequent cancers among males, and a poor survival rate reflects problems with aggressiveness and chemo-resistance. Accumulating evidence indicates that SIRT1 is involved in bladder cancer tumorigenesis and is positively associated with chemo-resistance and poor prognosis. We recently synthesized water-soluble chemical derivatives of heliomycin, an antibiotic from Streptomyces resistomycificus, and demonstrated that they possess anticancer properties. In this present study, we used the cellular thermal shift assay (CETSA) in T24 bladder cancer cells to show that heliomycin (designated compound (H1)) and its 4-(tert-butylamino)methyl derivative (HD2) directly engaged with SIRT1 in the native cellular environment, whereas another derivative (HD3) did not. Upon binding, heliomycin downregulated SIRT1 protein expression without altering its transcript level, and subsequently induced autophagy. Interestingly, the derivative (HD2) triggered apoptosis. The interaction between SIRT1 protein and heliomycin or its derivatives was also speculated by a molecular docking simulation, suggesting heliomycin (H1) and derivative (HD2) acting with the different binding modes to SIRT1. Given the increased water-solubility, hydrogen bonds were found on Ala262 and Ile347 residues in the docked complex of derivative (HD2) to produce more steady interaction and initiate signaling pathways that were not observed in the case of heliomycin. Meanwhile, it is evident that derivative (HD3) did not engage with SIRT1 by CETSA or molecular docking studies, nor did it downregulate SIRT1 expression. Taken together, these findings clearly show that SIRT1 is targeted and downregulated by heliomycin and its water-soluble 4-aminomethylated derivative (HD2) possibly through autophagic and/or proteasomal degradation, leading to cell death and growth suppression of T24 bladder cancer cells.


Energy restriction combined with green coffee bean extract affects serum adipocytokines and the body composition in obese women.
Obesity has become a public health problem and is a cause of some preventable illnesses. Among several methods for treating obesity, the use of food supplements is highly common. A commonly used food supplement is green coffee bean extract. The objective of this study was to evaluate the efficacy of green coffee bean extract combined with an energy-restricted diet on the body composition and serum adipocytokines in obese women. In this randomised clinical trial, 64 obese women aged 20-45 years were selected and divided into two groups: an intervention group (receiving 400 mg green coffee bean extract for 8 weeks) and control group (receiving placebo). All participants were on an energy-restricted diet. The body composition, leptin, adiponectin, lipid profile, free fatty acids (FFAs), and fasting blood sugar were compared between the two groups. We observed significant reductions in the body weight, body mass and fat mass indices, and waist-to-hip circumference ratio in both groups; however, the decrease was higher in the intervention group. Moreover, serum total cholesterol, low-density lipoprotein, leptin, and plasma free fatty acids significantly decreased in the intervention group (p<0.05) after adjustment for energy and fibre intake. The serum adiponectin concentration significantly increased in the intervention group (p<0.05). Green coffee bean extract combined with an energy-restricted diet affects fat accumulation and lipid metabolism and is thus an inexpensive method for weight control in obese people.


Disruption of Claudin-1 Expression by miRNA-182 Alters the Susceptibility to Viral Infectivity in HCV Cell Models.
HCV entry involves a complex interplay between viral and host molecules. During post-binding interactions, the viral E2 complexes with CD81 receptor for delivery to the tight junction proteins CLDN1 and OCLN, which aid in viral internalization. Targeting HCV entry receptors represents an appealing approach to inhibit viral infectivity. This study aimed at investigating the impact of targeting CLDN1 by microRNAs on HCV infectivity. miR-155 was previously shown to target the 3'UTR of CLDN1 mRNA. Therefore, miR-155 was used as a control in this study. In-silico analysis and luciferase reporter assay were utilized to identify potential targeting miRNAs. The impact of the identified miRNAs on CLDN1 mRNA and protein expression was examined by qRT-PCR, indirect immunofluorescence and western blotting, respectively. The role of the selected miRNAs on HCV infectivity was assessed by measuring the viral load following the ectopic expression of the selected miRNAs. miR-182 was identified in-silico and by experimental validation to target CLDN1. Both miR-155 and miR-182 inhibited CLDN1 mRNA and protein expression in infected Huh7 cells. Ectopic expression of miR-155 increased, while miR-182 reduced the viral load. In conclusion, despite repressing CLDN1, the impact of miR-155 and miR-182 on HCV infectivity is contradictory. Ectopic miR-182 expression is suggested as an upstream regulator of the entry factor CLDN1, harnessing HCV infection.


PSF and p54nrb bind a conserved stem in U5 snRNA.
PTB-associated splicing factor (PSF) has been implicated in both early and late steps of pre-mRNA splicing, but its exact role in this process remains unclear. Here we show that PSF interacts with p54nrb, a highly related protein first identified based on cross-reactivity to antibodies against the yeast second-step splicing factor Prpl8. We performed RNA-binding experiments to determine the preferred RNA-binding sequences for PSF and p54nrb, both individually and in combination. In all cases, iterative selection assays identified a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. Filter-binding assays and RNA affinity selection experiments demonstrated that PSF and p54nrb bind U5 snRNA with both the sequence and structure of stem 1b contributing to binding specificity. Sedimentation analyses show that both proteins associate with spliceosomes and with U4/U6.U5 tri-snPNP.


Systemic Inflammatory Biomarkers and Chest CT Findings as Predictors of Acute Limb Ischemia Risk, Intensive Care Unit Admission, and Mortality in COVID-19 Patients.
Background: Numerous tools, including inflammatory biomarkers and lung injury severity scores, have been evaluated as predictors of thromboembolic events and the requirement for intensive therapy in COVID-19 patients. This study aims to verify the predictive role of inflammatory biomarkers [monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic inflammatory index (SII), Systemic Inflammation Response Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI)] and the CT Severity Score in acute limb ischemia (ALI) risk, intensive unit care (ICU) admission, and mortality in COVID-19 patients.; Methods: The present study was designed as an observational, analytical, retrospective cohort study and included all patients older than 18 years of age with a diagnosis of COVID-19 infection, confirmed through real time-polymerase chain reaction (RT-PCR), and admitted to the County Emergency Clinical Hospital of Targu-Mureș, Romania, and Modular Intensive Care Unit of UMFST "George Emil Palade" of Targu Mures, Romania between January 2020 and December 2021. Results: Non-Survivors and "ALI" patients were associated with higher incidence of cardiovascular disease [atrial fibrillation (AF) p = 0.0006 and p = 0.0001; peripheral arterial disease (PAD) p = 0.006 and p < 0.0001], and higher pulmonary parenchyma involvement (p < 0.0001). Multivariate analysis showed a high baseline value for MLR, NLR, PLR, SII, SIRI, AISI, and the CT Severity Score independent predictor of adverse outcomes for all recruited patients (all p < 0.0001). Moreover, the presence of AF and PAD was an independent predictor of ALI risk and mortality. Conclusions: According to our findings, higher MLR, NLR, PLR, SII, SIRI, AISI, and CT Severity Score values at admission strongly predict ALI risk, ICU admission, and mortality. Moreover, patients with AF and PAD had highly predicted ALI risk and mortality but no ICU admission.


A learning module in hair restoration surgery: A simple and economic method to learn all steps of strip method of hair follicles harvesting and implantation.
There is a global increase in demand for hair transplant as well as increasing demand for trained assistants and surgeons. It is a fact that permanent donor hair follicles are limited and any loss during learning is permanent and irreversible, so there is no place to learn and/or practice on a patient. To develop a learning module in hair restoration surgery to learn all steps of strip method of hair follicles harvesting and methods of implantation. In this learning module, the materials used are paper, pencil, plant leaf, foam and thread. The last step is on goat skin. Module has been divided into multiple steps. The first step is training of microsurgery position, the second step is training of movement at wrist using paper and pencil, the third step is strip harvesting and slivering on foam model, the fourth step is learning of follicle dissection on leaf model, the fifth step is thread follicle implantation on leaf bed. After practising on non-living model finally, all steps are practised on goatskin, starting from slivering, follicle dissection and implantation of goat follicles on leaf. This is very economical and user-friendly system to learn all steps of strip method of hair follicle harvesting and methods of implantation as well. The materials used are available around us and anyone can learn as well as train his or her technicians in very short time.


Predictors of pneumonia in trauma patients with pulmonary contusion.
The purpose of this article was to determine assessable risk levels for pneumonia in trauma patients with pulmonary contusion. A retrospective review and analysis of national trauma data of patients with pulmonary contusion were identified to develop a risk assessment model. Trauma data for 2007 were used to determine risk factors for subsequent complication of pneumonia in pulmonary contusion patients. Available patient comorbidities were considered in model development. Next, 2008 data were used to test and finalize model. Pneumonia risk was categorized into 3 ordinal levels, based on equal-sized proportions of pulmonary contusion patients. Significant risk factors for pneumonia included age, gender, pulse rate, systolic blood pressure, obesity, Glasgow Coma Scale motor score, and ventilation on admission. The final risk adjustment model had good fit and discrimination. Study analyses used more than 40 000 trauma patient data to devise assessable risk levels for pneumonia in pulmonary contusion diagnosed patients. Study data can assist in direction of care and triaging of urgent care patients at risk of pneumonia, possibly leading to mitigation and prevention of pneumonia in at risk patients. Further review of study outcomes should occur to fully understand applicability and usefulness in urgent settings.


Gastroesophageal reflux disease and vocal disturbances.
Gastroesophageal reflux disease is a chronic disease in which gastroduodenal contents reflux into the esophagus. The clinical picture of gastroesophageal reflux disease is usually composed by heartburn and regurgitation (typical manifestations). Atypical manifestations (vocal disturbances and asthma) may also be complaint. To analyse the clinical, endoscopic, manometric and pHmetric aspects of patients suffering from gastroesophageal reflux disease associated with vocal disturbances. Fifty patients with gastroesophageal reflux disease were studied, including 25 with vocal disturbances (group 1 - G1) and 25 without these symptoms (group 2 - G2). All patients were submitted to endoscopy, manometry and esophageal pHmetry (2 probes). The group 1 patients were submitted to videolaryngoscopy. Endoscopic findings: non-erosive reflux disease was observed in 95% of G1 patients and 88% of G2. Videolaryngoscopy: vocal fold congestion, asymmetry, nodules and polyps were observed in G1 patients. Manometric findings: pressure in the lower esophageal sphincter (mm Hg): 11.6 ± 5.2 in G1 and 14.0 ± 6.2 in G2 (P = 0.14); pressure in the upper esophageal sphincter (mm Hg): 58.4 ± 15.9 in G1 and 69.5 ± 30.7 in the controls. pHmetric findings: De Meester index: 34.0 ± 20.9 in G1 and 15.4 ± 9.4 in G2 (P<0.001); number of reflux episodes in distal probe: 43.0 ± 20.4 in G1 and 26.4 ± 17.2 in G2 (P = 0.003); percentage of time with esophageal pH value lower than 4 units (distal sensor): 9.0% ± 6.4% in G1 and 3.4% ± 2.1% in G2 (P<0.001); number of reflux episodes in proximal probe: 7.5 ± 10.9 in G1 and 5.3 ± 5.7 in G2 (P = 0.38); percentage of time with esophageal pH values lower than 4 units (Proximal probe): 1.2 ± 2.7 in G1 and 0.5 ± 0.7 in G2 (P = 0.21). 1) The clinical, endoscopic, and manometric findings observed in patients with vocal disturbance do not differ from those without these symptoms; 2) gastroesophageal reflux intensity is higher in patients with vocal disturbance; 3) patients without vocal disturbance can also present reflux episodes in the proximal probe.


Evaluation of Association of Vitamin D Receptor Genetic Polymorphism with Severe Chronic Periodontitis in an Ethnic Tamilian Population.
Periodontitis is a multifactorial disease characterized by inflammatory responses to increased levels of subgingival pathogens, resulting in connective tissue destruction and alveolar bone loss. The susceptibility of an individual is determined by the complex interplay of the host, genetic, and environmental factors. Vitamin D, a secosteroid hormone, interacts with its nuclear receptor vitamin D receptor (VDR) to regulate crucial biological processes, such as bone metabolism and immune function modulation. Various studies have been conducted in different populations to analyze the association of VDR gene polymorphisms with chronic periodontitis, as these polymorphisms have been demonstrated to play vital roles in the pathogenesis of other diseases. The aim of the present study was to determine the prevalence and association of the VDR TaqI gene polymorphism with severe chronic periodontitis in an Ethnic Tamilian population. A total of 140 subjects were recruited for the study, of which 70 were diagnosed with severe chronic periodontitis and 70 had healthy gums. Each subject's medical and dental histories were taken, and periodontal examinations were performed. Genomic DNA was extracted and genotyping of the VDR gene at the TaqI site was carried out using polymerase chain reaction/restriction fragment length polymorphism. The frequencies of genotypes and alleles were analyzed between the study groups. The frequency of homozygous TT genotype was 40%, for both the severe chronic periodontitis and the healthy control groups. The distribution of heterozygous Tt genotype was 42.9% in the severe chronic periodontitis group and 47.1% in the healthy control group. The frequency of homozygous tt genotype was 17.1% in the severe chronic periodontitis group and 12.7% in the healthy control group. Although the prevalence of genotype tt and t allele was slightly increased in severe chronic periodontitis patients compared with healthy controls, the frequency of VDR genotype between the study groups was not statistically significant (p-value = 0.751). This present study performed in an Ethnic Tamilian population does not support an association between either of the TaqI alleles within the VDR gene and Severe Chronic Periodontitis.


Multicolor Photo-Crosslinkable AIEgens toward Compact Nanodots for Subcellular Imaging and STED Nanoscopy.
Aggregation induced emission (AIE) has attracted considerable interest for the development of fluorescence probes. However, controlling the bioconjugation and cellular labeling of AIE dots is a challenging problem. Here, this study reports a general approach for preparing small and bioconjugated AIE dots for specific labeling of cellular targets. The strategy is based on the synthesis of oxetane-substituted AIEgens to generate compact and ultrastable AIE dots via photo-crosslinking. A small amount of polymer enriched with oxetane groups is cocondensed with most of the AIEgens to functionalize the nanodot surface for subsequent streptavidin bioconjugation. Due to their small sizes, good stability, and surface functionalization, the cell-surface markers and subcellular structures are specifically labeled by the AIE dot bioconjugates. Remarkably, stimulated emission depletion imaging with AIE dots is achieved for the first time, and the spatial resolution is significantly enhanced to ≈95 nm. This study provides a general approach for small functional molecules for preparing small sized and ultrastable nanodots.


Prostatic Abscess on Xanthogranulomatous Prostatitis: Uncommon Complication of an Uncommon Disease.
Xanthogranulomatous prostatitis is a rare benign inflammatory process of the prostate. Only few cases have been reported in the English literature. Xanthogranulomatous prostatitis is usually an incidental finding after needle biopsy or transurethral resection of the prostate in patients suffering from low urinary tract symptoms. We report the case of a 59-years-old patient diagnosed with prostatic abscess managed by transurethral resection of the prostate. Histopathological examination of resected prostatic tissue revealed abscessed xanthogranulomatous prostatitis with no evidence of malignancy. Xanthogranulomatous prostatitis presenting as a prostatic abscess is a rare finding. To the best of our knowledge our case represents the fourth case of xanthogranulomatous prostatitis presenting as prostatic abscess reported in the English literature so far.


Decalcification of a choroidal osteoma.
A 56-year-old man presented with a clearly defined orange tumour in the posterior pole of his left eye. A choroidal osteoma was suspected, and ultrasonography confirmed the diagnosis. Fluorescein angiography demonstrated subretinal neovascularisation on the nasal edge of the tumour, which was treated with krypton laser photocoagulation twice. Recurrent subretinal neovascularisation occurred one year later and was not amenable to treatment. Three years after the patient first presented, thinning of the tumour was noted on follow-up examination. During the next 15 months the tumour completely disappeared, leaving an area of retinal pigment epithelial and choroidal atrophy. Total decalcification of the choroidal osteoma was demonstrated by ultrasonography.


Comparative anatomy of embryogenesis in three species of Podostemaceae and evolution of the loss of embryonic shoot and root meristems.
During embryogenesis in angiosperms, the embryonic shoot and root meristems are created at opposite poles of the embryo, establishing a vertical body plan. However, the aquatic eudicot family Podostemaceae exhibits an unusual horizontal body plan, which is attributed to the loss of embryonic shoot and root meristems. To infer the embryogenetic changes responsible for the loss of these meristems, we examined the embryogenesis of three podostemads with different meristem characters, that is, Terniopsis brevis with distinct shoot and root meristems, Zeylanidium lichenoides with reduced shoot and no root meristems, and Hydrobryum japonicum with no shoot and no root meristems. In T. brevis, as in other eudicots, the putative organizing center (OC) and L1 layer (=the epidermal cell layer) arose to generate a distinct shoot meristem initial, and the hypophysis formed the putative quiescent center (QC) of a root meristem. Z. lichenoides had a morphologically unrecognizable shoot meristem, because a distinct L1 layer did not develop, whereas the putative OC precursor arose normally. In H. japonicum, the vertical divisions of the apical cells of eight-cell embryo prevented putative OC initiation. In Z. lichenoides and H. japonicum, the putative QC failed to initiate because the hypophysis repeated longitudinal divisions during early embryogenesis. Based on their phylogenetic relationships, we infer that the conventional embryonic shoot meristem was lost in Podostemaceae via two steps, that is, the loss of a distinct L1 layer and the loss of the OC, whereas the loss of the embryonic root meristem occurred once by misspecification of the hypophysis.


Efficacy of amikacin combinations for nocardiosis.
We isolated five bacterial strains from patients diagnosed as having nocardiosis. Bacterial species were identified based on the similarities in the nucleotide sequences of 16S ribosomal RNAs. Three of the five strains were identified as Nocardia asteroids, but unexpectedly other two were Streptomyces hygroscopicus and Rothia dentocariosa. The latter two species are not members of the family Nocardiaceae. We investigated the susceptibilities of these five strains to the following nine antimicrobial agents: trimethoprim/sulfamethoxazole (TMP/SMX), minocycline (MINO), erythromycin (EM), amikacin (AMK), cefotaxime (CTX), faropenem (FRPM), imipenem (IPM), ciprofloxacin (CPFX), and sparfloxacin (SPFX). The minimum inhibitory concentration (MIC) ranges (mg/ml) were as follows: TMP-SMX, 4- > 32; MINO, 0.125-8; EM, < or = 0.016- > 32; AMK, 1-2; CTX, 0.063- > 32; FRPM, 0.063-16; IPM, 0.125-2; CPFX, 4-32; and SPFX, 0.5-16. Moreover, the synergistic effects of AMK in combination with each of TMP-SMX, MINO, EM, CTX, IPM, and SPFX were investigated by checkerboard synergy testing. No antagonism was recognized for the three N. asteroides strains. Synergistic and additive effects were observed for the combinations of AMK with CTX, IPM, or SPFX.


Mental health literacy: empowering the community to take action for better mental health.
For major physical diseases, it is widely accepted that members of the public will benefit by knowing what actions they can take for prevention, early intervention, and treatment. However, this type of public knowledge about mental disorders (mental health literacy) has received much less attention. There is evidence from surveys in several countries for deficiencies in (a) the public's knowledge of how to prevent mental disorders, (b) recognition of when a disorder is developing, (c) knowledge of help-seeking options and treatments available, (d) knowledge of effective self-help strategies for milder problems, and (e) first aid skills to support others affected by mental health problems. Nevertheless, there is evidence that a range of interventions can improve mental health literacy, including whole-of-community campaigns, interventions in educational settings, Mental Health First Aid training, and information websites. There is also evidence for historical improvements in mental health literacy in some countries. Increasing the community's mental health literacy needs to be a focus for national policy and population monitoring so that the whole community is empowered to take action for better mental health.


Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy.
Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.


The role of amifostine as a radioprotector.
Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. Radiation doses that can be delivered, without causing severe damage to surrounding normal tissues, can be insufficient to eradicate a tumor. Agents have been developed to protect normal tissue from the toxicities of radiation. The aminothiol amifostine (Ethyol) is the subject of extensive research as a protector. Several studies have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. This article reviews the physicochemical basis of radiation therapy on biologic tissues and the mechanisms responsible for the protective effects of amifostine. The increasing body of biochemical, preclinical, and clinical data can justify the use of protectors such as amifostine with radiotherapy to provide improved therapeutic efficacy and quality of life for the patient. This article will review the current understanding of the nature of toxicity resulting from radiation therapy and the benefits that can be derived from using protection to increase the tolerance of normal tissue to radiation damage.


The chloroform fraction of Solanum nigrum suppresses nitric oxide and tumor necrosis factor-α in LPS-stimulated mouse peritoneal macrophages through inhibition of p38, JNK and ERK1/2.
Solanum nigrum L., commonly known as black nightshade, is used worldwide for the treatment of skin and mucosal ulcers, liver cirrhosis and edema. We aimed to determine the anti-inflammatory active fraction of S. nigrum by serial extractions. S. nigrum was first extracted with methanol, then fractionated with chloroform and water. The effects of S. nigrum fractions, diosgenin and α-solanine on LPS/interferon-gamma-induced nitric oxide (NO) and inducible NO synthase (iNOS), or LPS-induced tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, in mouse peritoneal macrophages were determined. Western blotting analysis was used to detect LPS-induced phosphorylation of p38, JNK and ERK1/2. The chloroform fraction of S. nigrum was cytotoxic in a time and concentration dependent manner; however, the methanol and water fractions were not. The chloroform fraction reduced NO through inhibition of iNOS synthesis and inhibited TNF-α and IL-6 at the level of protein secretion; the methanol and water fractions showed a weak or no effect. The chloroform fraction also suppressed p38, JNK and ERK1/2. Diosgenin and α-solanine were cytotoxic at a high concentration. In particular, diosgenin was able to inhibit TNF-α and IL-6, but both compounds did not affect LPS-induced iNOS expression. These results indicate that the anti-inflammatory compounds of S. nigrum exist preferentially in the nonpolar fraction, ruling out the possibility that diosgenin and α-solanine are the likely candidates. The inhibition of iNOS, TNF-α and IL-6 by the chloroform fraction may be partly due to the suppression of p38, JNK and ERK1/2. Further study is required to identify the active compounds of S. nigrum.


Grebe-Quelce-Salgado chondrodystrophy: prenatal diagnosis of two new cases in unrelated families in Southern Brazil.
Grebe-Quelce-Salgado chondrodystrophy is an autosomal recessive non-lethal skeletal dysplasia. Affected individuals have normal head, neck, and trunk skeleton, relatively normal humeri and femora, short and deformed radii, ulnae, tibiae, and fibulae, and severe abnormalities of hands and feet. Polydactyly is frequent. Digits present as globular appendages and are characteristic of the condition. The disease is caused by a missense mutation in the gene encoding cartilage-derived morphogenetic protein-1 (CDMP-1). Most cases described in the literature are from Brazil and, among these, all had ancestors from a particular region in the state of Bahia. We describe two cases of Grebe-Quelce-Salgado chondrodystrophy visualized by prenatal ultrasound. The patients presented in this report do not descend from the population of Bahia and, to our knowledge, case two is the only case with prenatal clinical diagnosis in a family with no previously affected children.


Central Versus Peripheral Invasive Arterial Blood Pressure Monitoring in Liver Transplant Surgery.
Introduction Invasive blood pressure monitoring is essential in liver transplant surgery due to expected major hemodynamic shifts. The use of central versus peripheral arterial access, however, is institution-dependent, which can affect clinical decisions regarding vasopressor therapy. Although there are studies that demonstrate inconsistencies based on arterial cannulation sites, few studies have compared femoral and radial artery blood pressures in patients undergoing liver transplant surgery. To our knowledge, there are no studies investigating the differences between continuous minute-to-minute femoral and radial artery measurements during all three phases of liver transplant surgery. Objective The main objective of this study was to evaluate for any differences between central and peripheral blood pressure measurements in liver transplant surgery and to assess for any correlation between vasopressor infusion dose and femoral-arterial pressure differences. Methods In this retrospective study, we reviewed and studied the data of 61 patients with American Society of Anesthesiologists (ASA) grade 4 who underwent liver transplant surgery at Loma Linda University Medical Center between January and December of 2019. All patients had both femoral and radial arterial lines placed for liver transplant surgery. Femoral and radial arterial blood pressure values were obtained continuously over 60 minutes in the pre-anhepatic phase, 45 minutes during the anhepatic phase, and 60 minutes into the neo-hepatic phase. Vasopressor infusion doses were also recorded for each patient during these time frames. Results This pilot study found statistically significant differences between the mean femoral and radial systolic blood pressure (SBP; p < 0.0001), diastolic blood pressure (DBP; p < 0.0001), and mean arterial pressure (MAP; p < 0.0001) during all phases of liver transplantation. The meanSBP and MAP differences between femoral and radial arteries were highest (femoral blood pressure reading higher than radial blood pressure measurements) in the late anhepatic and early neo-hepatic phases with SBP differences of 20.8 ± 0.8 mmHg and 22.8 ± 0.8 mmHg, respectively, and MAP differences of 10.0 ± 0.4 mmHg and 9.8 ± 0.4 mmHg, respectively. Higher vasopressor infusion doses were strongly associated with greater differences in femoral-radial SBP and MAP measurements (r = 0.69 for vasopressin, 0.68 for norepinephrine, and 0.68 for epinephrine; p < 0.0001) during the anhepatic phase. Conclusions Peripheral invasive blood pressure monitoring may result in underestimation of the central blood pressure, as was seen in all phases of liver transplantation. This may lead to excessive vasopressor use with potentially adverse effects. Although the cause for the difference between femoral and radial artery measurements is unclear, increasing vasopressor infusion dosages appears to contribute. Femoral artery blood pressure monitoring allows clinicians to interpret hemodynamic status and administer appropriate vasopressors more accurately.


Talcosis associated with IV abuse of oral medications: CT findings.
Our objective was to evaluate the CT appearance of talcosis associated with IV abuse of oral medications and to compare the findings of talcosis related to methylphenidate with those findings seen with other drugs. The CT scans of 12 patients with talcosis (seven men, five women), 33-54 years old (mean age, 44 years), were analyzed retrospectively. Seven patients had abused methylphenidate; five patients had no history of abuse. The diagnosis of talcosis was made histologically in 11 patients and at funduscopy in one patient. CT was performed with 1- to 1.5-mm collimation (n = 10 patients) or 5- to 10-mm collimation (n = 2). The predominant abnormalities seen on CT consisted of a diffuse fine nodular pattern (n = 2), a combination of nodules and lower lobe panacinar emphysema (n = 3), and ground-glass attenuation (n = 2). Emphysema was the only abnormality seen in the remaining five patients (lower lobe panacinar, n = 4; upper lobe centrilobular, n = 1). No significant difference in the prevalence of nodules and ground-glass attenuation was seen between the methylphenidate and non-methylphenidate groups. Lower lobe panacinar emphysema was more common in methylphenidate abusers (six [86%] of seven patients) than in non-mnethylphenidate drug abusers (one [20%] of five, p<0.05, Fisher's exact test). The CT manifestations of talcosis consist of a fine micronodular pattern, ground-glass attenuation, and emphysema. A significantly increased prevalence of lower lobe panacinar emphysema is seen in IV drug addicts who abuse methylphenidate.


Filamentous hemagglutinin adhesin FhaB limits A.baumannii biofilm formation.
Increased resistance and survival, as well as immune evasion, play a significant role in the pathogenicity of Acinetobacter baumannii. Here, we report on the adhesion of the bacterium to epithelial cells and formation of biofilm on abiotic surfaces. We identificed autotransporter (AT) genes that encode homologues (Fha-like) of the two-partner secretion system (TPS) in A.baumannii (ATCC19606) which we designate as FhaB (exoprotein) and FhaC (transporter) and demonstrate that these novel genes, are under the control of distinct regulatable promoters within either the same (FhaBC) or two distinct (FhaB and FhaC) cells. The expression of this gene in outer membrane protein (OM) showed them to be deficient in the adherence to A546 cells. FhaB is involved in hydrophobicity of A. baumannii ATCC19606 while FhaBC is associated with biofilm formation. The vaccinogenic potential of FHA-like proteins offers use of these targets as novel therapeutic strategies to limit A.baumannii associated morbidity and mortality.


Four decades of pulmonary tuberculosis in deceased South African miners: trends and determinants.
We investigated trends and determinants of pulmonary tuberculosis (PTB) in deceased South African miners. Statutory autopsies are performed on miners for occupational lung disease compensation, irrespective of cause of death. Data were extracted from the PATHAUT (Pathology Automation System) autopsy database. PTB trends were analysed and explanatory variables (year of autopsy, age at death, gold employment duration, silicosis and HIV) were evaluated using binary logistic regression modelling. Analyses were stratified by population group because of racial differences in socioeconomic status, employment patterns and access to facilities for autopsies. The analyses were segmented to represent the pre-HIV (1975-1989), rapid HIV spread (1990-2004) and antiretroviral therapy (2005-2014) periods. The proportions of men with PTB at autopsy increased from 4.62% in 1975 to 27.18% in 2014 in black miners, and from 2.07% to 5.19% in white miners, with peaks in 2007 (43.12% and 9.51%, respectively). The magnitude and significance of adjusted ORs of determinants differed by population group and calendar period. PTB was largely associated with silicosis, increasing gold employment duration and year of autopsy (a surrogate for unmeasured confounders, such as unknown HIV status and tuberculosis transmission). Changes in PTB time trends and determinants reflect the complex social and political environment in which mining occurs. Silica dust reduction remains a key intervention for tuberculosis reduction, together with tuberculosis and HIV treatment and management. The autopsy data provide reliable information to monitor progress towards the achievement of industry and national targets to reduce tuberculosis.


[Treatment of tinea unguium with terbinafine: an open study comparing twelve weeks and twenty-four weeks of continuous terbinafine therapy, and determination of terbinafine level in the target nails].
The study protocol was approved by the Ethical Committee of Sakai Municipal Hospital. A total of 40 outpatients with tinea unguium of the toenails, fingernails or both took part after giving voluntary written informed consent. Inclusion criteria were suggestive clinical appearance, a positive KOH preparation and an opaqueness of more than 50% of the nail length. The patients received 125 mg terbinafine once a day. The medication was taken after the evening meal and treatment was continued for 12 weeks. Medication stopped in twenty patients who responded well and a follow-up study was continued for 64 weeks. In the other 20 patients, medication was continued for 24 weeks and the follow-up study continued for 64 weeks. At 4-week intervals, the patients were evaluated for their clinical and mycological statuses and adverse reactions. Clipping of distal nail samples, including any attached subungual tissue, was done using nail clippers at 4-week intervals after cessation of therapy and the level of terbinafine was measured in the laboratory. No adverse reactions were detected. Tinea unguium of fingernails (1) and the third toes (2) were cured easily in the short term in the 12 week therapy group. One case in the 24 week therapy group was excluded because systemic steroid therapy was started for bullous pemphigoid at 32 weeks. The results of treatment of big toe onychomycosis were compared between the 12 week (17) and the 24 week (19). In the former group, 9 (52.9%) showed complete cure and 8 (47.1%) showed relapse or worse after cessation of therapy was. In 24 week therapy group, complete cure was achieved in 14 (73.7%) and relapse or worse in 5 (26.3%). The cure rate between the 2 groups was statistically not significant. Terbinafine was detected in the target nails up to 24 weeks after cessation of medication in both groups. Onychomycosis or tinea pedis reappeared in a few cases 12 to 16 weeks after medication ceased in the 12 week group. Topical antimycological therapy is necessary after cessation of oral terbinafine.


[Genetic analysis of two fetuses with congenital heart defects and 3q microdeletion].
To determine the nature of genomic copy number variations (CNVs) in two fetuses with congenital heart defects (CHD) and explore the correlation between 3q microdeletions and CHD. Genomic DNA was extracted from fetal umbilical cord tissue, and chromosome copy number variations were detected by low coverage whole genome sequencing. Both fetuses had microdeletions of the long arm of chromosome 3. Fetus 1 had ventricular septal defect, cleft lip and palate, and a 1.66 Mb deletion on 3q29. The deleted region encompassed all of the critical genes for 3q29 microdeletion syndrome. Fetus 2 had overriding aorta, ventricular septal defect, and a novel 240 kb deletion on 3q28. 3q29 microdeletion may result in CHD in combination with cleft lip and palate. Genomic CNVs can be detected by low coverage whole genome sequencing.


Effects of various disaccharide adaptations on recombinant IgA1 production in CHO-K1 suspension cells.
Immunoglobulin A (IgA) has been showing potential as a new therapeutic antibody. However, recombinant IgA suffers from low yield. Supplementation of the medium is an effective approach to improving the production and quality of recombinant proteins. In this study, we adapted IgA1-producing CHO-K1 suspension cells to a high concentration (150 mM) of different disaccharides, namely sucrose, maltose, lactose, and trehalose, to improve the production and quality of recombinant IgA1. The disaccharide-adapted cell lines had slower cell growth rates, but their cell viability was extended compared to the nonadapted IgA1-producing cell line. Glucose consumption was exhausted in all cell lines except for the maltose-adapted one, which still contained glucose even after the 9th day of culturing. Lactate production was higher among the disaccharide-adapted cell lines. The specific productivity of the maltose-adapted IgA1-producing line was 4.5-fold that of the nonadapted line. In addition, this specific productivity was higher than in previous productions of recombinant IgA1 with a lambda chain. Lastly, secreted IgA1 aggregated in all cell lines, which may have been caused by self-aggregation. This aggregation was also found to begin inside the cells for maltose-adapted cell line. These results suggest that a high concentration of disaccharide-supplemented induced hyperosmolarity in the IgA1-producing CHO-K1 cell lines. In addition, the maltose-adapted CHO-K1 cell line benefited from having an additional source of carbohydrate. The online version contains supplementary material available at 10.1007/s10616-023-00571-5.


AMOEBA Force Field Trajectories Improve Predictions of Accurate pKa Values of the GFP Fluorophore: The Importance of Polarizability and Water Interactions.
Precisely quantifying the magnitude, direction, and biological functions of electric fields in proteins has long been an outstanding challenge in the field. The most widely implemented experimental method to measure such electric fields at a particular residue in a protein has been through changes in pKa of titratable residues. While many computational strategies exist to predict these values, it has been difficult to do this accurately or connect predicted results to key structural or mechanistic features of the molecule. Here, we used experimentally determined pKa values of the fluorophore in superfolder green fluorescent protein (GFP) with amino acid mutations made at position Thr 203 to evaluate the pKa prediction ability of molecular dynamics (MD) simulations using a polarizable force field, AMOEBA. Structure ensembles from AMOEBA were used to calculate pKa values of the GFP fluorophore. The calculated pKa values were then compared to trajectories using a conventional fixed charge force field (Amber03 ff). We found that the position of water molecules included in the pKa calculation had opposite effects on the pKa values between the trajectories from AMOEBA and Amber03 force fields. In AMOEBA trajectories, the inclusion of water molecules within 35 Å of the fluorophore decreased the difference between the predicted and experimental values, resulting in calculated pKa values that were within an average of 0.8 pKa unit from the experimental results. On the other hand, in Amber03 trajectories, including water molecules that were more than 5 Å from the fluorophore increased the differences between the calculated and experimental pKa values. The inaccuracy of pKa predictions determined from Amber03 trajectories was caused by a significant stabilization of the deprotonated chromophore's free energy compared to the result in AMOEBA. We rationalize the cutoffs for explicit water molecules when calculating pKa to better predict the electrostatic environment surrounding the fluorophore buried in GFP. We discuss how the results from this work will assist the prospective prediction of pKa values or other electrostatic effects in a wide variety of folded proteins.


Measurements of whole body retention of diphosphonate and other indices of bone metabolism in 125 normals: dependency on age, sex and glomerular filtration.
Measurements of 24-h whole body retention of 99m-Tc-MDP (WBR) has been performed in 125 normal volunteers, together with determinations of serum alkaline phosphatase, urinary hydroxyproline excretion and creatinine clearance. WBR decreased slightly from the 3rd to the 4th decade, after which it increased gradually in the older age-groups. Serum alkaline phosphatase followed an identical pattern, while the urinary hydroxyproline excretion demonstrated a marked but temporary rise in the post-menopausal age-groups. Finally, the creatinine clearance decreased gradually in the older age groups. Analysis of variance demonstrated that WBR varied independently with serum alkaline phosphatase and creatinine clearance, while no relationship between WBR and the hydroxyproline excretion was found. It seems likely that the increasing retention of diphosphonate in elderly persons reflects rising osteoblastic activity as well as decreasing glomerular filtration.


Ethnic differences in genetic susceptibility to atopy and asthma.
The genetics of asthma and atopy is complex, but can be approached by studies of both candidate genes and mapping of susceptibility loci. Genetic factors conferring susceptibility to disease may vary among ethnic groups. We present our experience with some candidate gene studies for asthma and atopy and susceptibility locus mapping for linkage to chromosome 5q.


Coupled plasma filtration adsorption for the treatment of a patient with acute respiratory distress syndrome and acute kidney injury: a case report.
Coupled plasma filtration adsorption (CPFA) is an extracorporeal blood purification therapy based on non-specific pro- and anti-inflammatory mediator adsorption on a special resin cartridge coupled with continuous veno-venous haemofiltration or continuous veno-venous haemodiafiltration and is one of the emerging treatments for septic patients. However, in the literature, there are limited data about its efficacy in treating patients with acute diseases but without the traditional criteria for sepsis. We describe the case of a 43-year-old male who developed acute respiratory distress syndrome secondary to pneumonia and acute kidney injury, whose clinical conditions rapidly improved after early CPFA therapy.


First report of intramolluscan stages of a gorgoderid digenean from a marine bivalve.
A survey of bivalves from Heron Island on the Great Barrier Reef, Australia, revealed a novel digenean infection in Lioconcha castrensis (Bivalvia: Veneridae). The cercaria has oral and ventral suckers, a dorsoventrally orientated stylet embedded in the oral sucker, penetration glands, and a large tail that is inflated at its base. This morphology is broadly consistent with that of previously described gorgoderid cercariae. Partial large subunit ribosomal RNA gene (D1-D3 domains) was sequenced and aligned with sequences from other gorgoderids and related families. Phylogenetic analysis also suggests that the species belongs to the Gorgoderinae. To our knowledge, this is the first report of a gorgoderid from a marine bivalve.


Spice: a legal marijuana equivalent.
Spice, an herbal mixture containing synthetic cannabinoids, is a legal drug increasingly abused by adolescents and young adults for its narcotic-like effects. A paucity of English language literature exists on the clinical effects of Spice use. A case report of substance-induced psychosis and a summary of available literature follows later.


RNA N1-methyladenosine regulator-mediated methylation modification patterns and heterogeneous signatures in glioma.
N1-methyladenosine (m1A) is ubiquitous in eukaryotic RNA and regulates mRNA translation. However, little is known about its regulatory role in glioma. Here, we identified 4 m1A modification-related patterns based on m1A regulators in the TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) cohorts. The differences in survival prognosis between different clusters were striking. In addition, stemness, genomic heterogeneity, tumor microenvironment (TME), and immune cell infiltration were also significantly different between the poor and best prognostic clusters. To reveal the underlying mechanism, differentially expressed genes (DEGs) between the poor and best prognostic clusters were identified, and then were integrated for weighted correlation network analysis (WGCNA). After Univariate Cox-LASSO-Multivariate Cox analyses, DEGs PLEK2 and ABCC3 were screened as the risk-hub genes and were selected to construct an m1A-related signature. Moreover, ABCC3 exacerbated glioma proliferation and was associated with temozolomide (TMZ) resistance. Overall, our study provided new insights into the function and potential therapeutic role of m1A in glioma.


Patterned few nanometer-thick silver films with high optical transparency and high electrical conductivity.
Transparent conductive electrodes (TCEs) are experimentally demonstrated using patterned few nanometer-thick silver films on zinc oxide-coated rigid and flexible substrates. The grid lines are completely continuous, but only 8.4 nm thick. This is the thinnest metallic grid we are aware of. Owing to the high transparency of both the grid lines and spacing, our TCE with an opening ratio (OR) as small as 36% achieves an average optical transmittance up to ∼90% in the visible regime, breaking the optical limits of both the unpatterned film counterpart and the thick grid counterpart (whose optical transmittance is determined by the OR). The small OR enables a low sheet resistance of ∼21.5 Ω sq-1. The figure of merit up to ∼17 kΩ-1 is superior to those of the unpatterned film counterpart, our fabricated 180 nm thick ITO, as well as most reported thick metal grid TCEs. Our ultrathin TCE, firmly attached to the substrate, is mechanically more flexible and more stable than the film counterpart and ITO. As a flexible transparent film heater, it achieves comparable or even superior heating performances with previously-reported heaters and performs well in a thermochromic test.


Characterization and Fine Mapping of qRPR1-3 and qRPR3-1, Two Major QTLs for Rind Penetrometer Resistance in Maize.
Stalk strength is one of the most important traits in maize, which affects stalk lodging resistance and, consequently, maize harvestable yield. Rind penetrometer resistance (RPR) as an effective and reliable measurement for evaluating maize stalk strength is positively correlated with stalk lodging resistance. In this study, one F2 and three F2:3 populations derived from the cross of inbred lines 3705I (the low RPR line) and LH277 (the high RPR line) were constructed for mapping quantitative trait loci (QTL), conferring RPR in maize. Fourteen RPR QTLs were identified in four environments and explained the phenotypic variation of RPR from 4.14 to 15.89%. By using a sequential fine-mapping strategy based on the progeny test, two major QTLs, qRPR1-3 and qRPR3-1, were narrowed down to 4-Mb and 550-kb genomic interval, respectively. The quantitative real-time PCR (qRT-PCR) assay was adopted to identify 12 candidate genes responsible for QTL qRPR3-1. These findings should facilitate the identification of the polymorphism loci underlying QTL qRPR3-1 and molecular breeding for RPR in maize.


The New Mexico aging process study (1979-2003). A longitudinal study of nutrition, health and aging.
In 1979, Dr. James S. Goodwin, M.D., assisted by Philip J. Garry, Ph.D., submitted a grant proposal to the United States Public Health Service/ National Institute on Aging (NIA) entitled, "A prospective study of nutrition in the elderly". This study was approved and funded by the NIA beginning in 1979. Initially, approximately 300 men and women over 65 years of age with no known medical illnesses and no prescription medications were selected for this study. The primary purpose of this multi disciplinary study, known in the literature as the New Mexico Aging Process Study (NMAPS), was to examine the role of nutrition and resultant changes in body composition and organ function in relation to the aging process and health status of the elderly. This was accomplished by following prospectively healthy elderly volunteers, obtaining in-depth information about dietary habits, lifestyle, body composition, organ function, cognitive status, vitamin metabolism, genetic markers, and biochemical measures of nutritional status and then examining these data in relationship to age and health status and changes in health status. Some of the specific aims of the study were modified over the course of this longitudinal study because of availability of University of New Mexico School of Medicine faculty with expertise in different areas of aging research. In 1988, Dr. Bruno Vellas from the University Hospital in Toulouse, France became an on-going visiting professor at the University of New Mexico School of Medicine. From 1988, until the study was terminated in 2003, Dr. Vellas has collaborated with the faculty involved in the NMAPS on a number of research projects. In this article, we provide information about the studies overall design and briefly describe some of the major finding of the NMAPS.


The effects of Vitamin D3 supplementation on Spermatogram and endocrine factors in asthenozoospermia infertile men: a randomized, triple blind, placebo-controlled clinical trial.
Evaluate the effects of vitamin D3 (VD3) on sperm parameters and endocrine markers in infertile men with asthenozoospermia. This randomized, triple-masking, placebo-controlled clinical trial conducted on 86 asthenozoospermia infertile men with serum 25 hydroxy vitamin D3 (25(OH)VD3) < 30 ng/ml in the infertility clinic of Ahvaz Jahad daneshgahi, Iran. Patients were randomly allocated to groups A and B, who received daily 4000 IU VD3 and matching placebo respectively for 3 months. Demographic data, dietary intake, physical activity, sun exposure, anthropometric indices, serum 25(OH)VD3, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), estradiol (E2),, sex hormone-binding globulin (SHBG), free androgen index (FAI = T/SHBG. 100), T/LH and T/E2 ratios, prolactin (PRO), parathyroid hormone (PTH), osteocalcin (OCN), phosphorus and sperm parameters were assessed. Three months VD3 supplementation with 4000 IU/day had no significant effects body weight, body mass index (BMI), waist circumference (WC), body fat (BF), serum, OCN, LH, FSH, T, E2, SHBG, PRO, T/E2 ratio, FAI, semen volume, sperm count and normal sperm morphology. It increases serum 25(OH)VD3, PTH and phosphorus and seminal and serum calcium, T/LH ratio and total and progressive sperm motility and decreased significantly compared to the baseline and placebo group. VD3 supplementation may affect sperm motility in men with asthenozoospermia and serum 25(OH)VD3 < 30 ng/ml. Iran Clinical Trials Registry, ID: IRCT20151128025274N4, registered on 28 March 2018, URL of trial registry record: https://www.irct.ir/trial/29983.


[Aseptic osteonecrosis of the femoral head in cancer patients with neuropathies caused by vincristine and vinblastine].
Aseptic osteonecrosis has been described in many and dissimilar pathologic conditions--most frequently as the aftermath of fractures or dislocations; in falciform anemia, obesity, alcoholism; in diseases requiring constant and heavy corticosteroid therapy, and also following renal transplantation. Many of these pathologies, especially alcoholism, diabetes, uremia, and collagen vascular diseases, have a common denominator: peripheral neuropathy, which is believed to be a pathogenetic factor supporting osteonecrosis. The authors analyze 3 cases of aseptic osteonecrosis of the femoral head in cancer patients treated with vincristine and/or vinblastine. Since in these subjects severe and persistent neuropathy preceded the onset of osteonecrosis, a possible relationship is postulated between the vincristine/vinblastine treatment and the onset of femoral head osteonecrosis, through the pathogenetic mechanism of peripheral neuropathy.


[Effects of anxiety on cardiorespiratory function].
The present study was undertaken to investigate the effect of anxiety on pulmonary function parameters and respiratory sinus arrhythmia (RSA) in healthy people under real-life conditions. This study consisted of two interrelated parts. During the first stage, eighty healthy students were examined in the following sequence: recording of heart rate variability (HRV) and respiration parameters at rest and shortly before real life stress. In a longitudinal study (the second stage), we assessed the profile of cardiorespiratory activity over 50 days in ten healthy women. Pulmonary function parameters like breath rate, tidal volume, forced expiratory volume in ones (FEV1), peak expiratory flow (PEF), forced expired flow at 25%, 50%, 75% of FVC, forced expired flow from 25-75% of FVC (FEF25-75%) and HRV measures (SDNN, RMSSD, pNN50, LF, HF, HFnorm, LF/HF ratio) of all subjects were tested. State anxiety was measured by Spielberger state anxiety inventory. Higher levels of state anxiety were associated with higher levels of breath rate, tidal volume and reduced HRV parameters, especially indicators of the RSA (HF and HFnorm) at baseline. These changes depend on the category of state anxiety: the group of students with a qualitative increase in state anxiety before examination has increased level of FEV1, PEF, forced expired flow at 25%, 50%, 75% of FVC, FEF25-75%. Less reactive students have no difference in respiratory parameters. We found a strong negative correlation between the level of HF at rest and state anxiety scores before examination. Longitudinal study found a negative correlation between RSA parameters and PEF, positive correlation between state anxiety and PEF of the majority those surveyed, except for two women with low levels of state anxiety and RSA indicators were in a narrow range. The variations of cardiorespiratory parameters during a longitudinal study depend on the changes of state anxiety. The higher level of state anxiety was associated with significant changes in RSA and the respiratory parameters. These results lend strong support to the notion that parasympathetic function is a critical physiological component of emotional processes.


Right-lateralized pain processing in the human cortex: an FMRI study.
Neuroimaging studies of human pain have revealed a widespread "pain matrix" distributed across both hemispheres of the brain. It is not resolved whether the pain matrix is biased toward one hemisphere, although behavioral and clinical data suggest that pain is perceived differently on the two sides of the body, and several neuroimaging studies suggest that pain processing in some regions of cortex may be lateralized toward the right hemisphere. The current study used fMRI in nine subjects to determine whether acute pain is preferentially processed in one cortical hemisphere. All cortical areas that were activated during the painful simulation were investigated, and several analytic approaches were used to directly compare activated regions to similar regions in the opposite hemisphere. Results indicated that four regions of the cortical pain matrix were activated either contralaterally (somatosensory cortex) or bilaterally (mid/posterior insula, anterior insula, and posterior cingulate). In addition, activation in five cortical regions during acute pain stimulation was localized either exclusively in the right hemisphere or was strongly lateralized to the right. These five areas were in the middle frontal gyrus, anterior cingulate, inferior frontal gyrus, medial/superior frontal gyri, and inferior parietal lobule. The location of some of these regions is consistent with the idea that there may be a right-lateralized attentional system to alert an organism to an infrequent, but behaviorally relevant, stimulus such as pain.


[Nutrition mode evaluation among University of Agriculture students in Szczecin in 2006. Part III. Coffee, tea, alcohol, smoking].
The objective of this inquiry study carried out in the midst of Szczecin University of Agriculture students, was to define the alcohol, coffee, tea and drugs consumption and also smoking. About 53-73% of the students declared to drink alcohol. Women preferred bear and men--wine. Smoking was practiced by 40% of men and 27% of women. Students from Szczecin preferred to drink coffee than tea. About 11% of the group of students has had episodic contact with drugs. Mostly with marihuana.