Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the Developing Mouse Prostate.
The prostate is a male accessory sex gland that produces secretions in seminal fluid to facilitate fertilization. Prostate secretory function is dependent on androgens, although the mechanism by which androgens exert their effects is still unclear. Polyamines are small cationic molecules that play pivotal roles in DNA transcription, translation and gene regulation. The rate-limiting enzyme in polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and increases upon administration of androgens. Furthermore, testosterone administered to castrated male mice restores prostate secretory activity, whereas administering testosterone and the ornithine decarboxylase inhibitor D,L-α-difluromethylornithine (DFMO) to castrated males does not restore prostate secretory activity, suggesting that polyamines are required for androgens to exert their effects. To date, no one has examined polyamines in prostate development, which is also androgen dependent. In this study, we showed that ornithine decarboxylase protein was expressed in the epithelium of the ventral, dorsolateral and anterior lobes of the adult mouse prostate. Ornithine decarboxylase protein was also expressed in the urogenital sinus (UGS) epithelium of the male and female embryo prior to prostate development, and expression continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly decreased the expression of developmental regulatory gene Notch1. Other genes implicated in prostatic development including Sox9, Wif1 and Srd5a2 were unaffected by DFMO. Together these results indicate that Odc1 and polyamines are required for androgens to exert their effect in mediating prostatic bud induction, and are required for the expression of a subset of prostatic developmental regulatory genes including Notch1 and Nkx3.1.


Evidence for decreased interaction and improved carotenoid bioavailability by sequential delivery of a supplement.
Despite the notable health benefits of carotenoids for human health, the majority of human diets worldwide are repeatedly shown to be inadequate in intake of carotenoid-rich fruits and vegetables, according to current health recommendations. To address this deficit, strategies designed to increase dietary intakes and subsequent plasma levels of carotenoids are warranted. When mixed carotenoids are delivered into the intestinal tract simultaneously, competition occurs for micelle formation and absorption, affecting carotenoid bioavailability. Previously, we tested the in vitro viability of a carotenoid mix designed to deliver individual carotenoids sequentially spaced from one another over the 6 hr transit time of the human upper gastrointestinal system. We hypothesized that temporally and spatially separating the individual carotenoids would reduce competition for micelle formation, improve uptake, and maximize efficacy. Here, we test this hypothesis in a double-blind, repeated-measure, cross-over human study with 12 subjects by comparing the change of plasma carotenoid levels for 8 hr after oral doses of a sequentially spaced carotenoid mix, to a matched mix without sequential spacing. We find the carotenoid change from baseline, measured as area under the curve, is increased following consumption of the sequentially spaced mix compared to concomitant carotenoids delivery. These results demonstrate reduced interaction and regulation between the sequentially spaced carotenoids, suggesting improved bioavailability from a novel sequentially spaced carotenoid mix.


Inactivation of aerosolized Bacillus atrophaeus (BG) endospores and MS2 viruses by combustion of reactive materials.
Accidental release of biological agents from a bioweapon facility may contaminate large areas, possibly causing disastrous environmental consequences. To address this issue, novel halogen-containing reactive materials are being designed with the added capability to inactivate viable airborne microorganisms. This study determined the efficiency of combustion products of such materials to inactivate aerosolized bacteria and viruses. Spores of Bacillus atrophaeus and MS2 viruses dispersed in dry air were exposed for subsecond time intervals to hydrocarbon flames seeded with different reactive powders so that bioaerosol particles interacted with the combustion products in a controlled high-temperature environment. The experiments were designed to quantify differences in the biocidal effects of different reactive material powders including Al and Mg, a B•Ti nanocomposite, an 8Al•MoO(3) nanothermite, and a novel Al•I(2) nanocomposite. Compared to pure hydrocarbon flame, powder-seeded flame (with no iodine) produced about an order of magnitude greater inactivation of bacterial spores. The iodine-containing material increased the spore inactivation by additional 2 orders of magnitude. The aerosolized MS2 viruses (generally not as stress-resistant as spores) were fully inactivated when exposed to combustion of either the iodinated or noniodinated powders. Overall, the study suggests a great biocidal potential of combustion products generated by novel iodine-containing nanocomposite materials.


Murine pulmonary response to chronic hypoxia is strain specific.
Information concerning the effects of genetic variation between different background strains on hemodynamic, morphometric, and gene expression response to hypoxia would be useful. Three strains of mice were kept in hypoxia and phenotyped followed by gene profiling analysis. Among the variables examined, hematocrit, right heart muscularization, and right ventricular systolic pressure showed a strain-specific effect. Increased gene expression of inflammatory, muscle, and angiogenesis genes were seen in all strains, though the specific genes changed varied among groups. These results suggest that different strains use different gene expression mechanisms to adapt to the challenge of chronic hypoxia, resulting in modified phenotypic changes.


Enlarging the gene-geography of Europe and the Mediterranean area to STR loci of common forensic use: longitudinal and latitudinal frequency gradients.
Tetranucleotide Short Tandem Repeats (STRs) for human identification and common use in forensic cases have recently been used to address the population genetics of the North-Eastern Mediterranean area. However, to gain confidence in the inferences made using STRs, this kind of analysis should be challenged with changes in three main aspects of the data, i.e. the sizes of the samples, their distance across space and the genetic background from which they are drawn. To test the resilience of the gradients previously detected in the North-Eastern Mediterranean to the enlargement of the surveyed area and population set, using revised data. STR genotype profiles were obtained from a publicly available database (PopAffilietor databank) and a dataset was assembled including >7000 subjects from the Arabian Peninsula to Scandinavia, genotyped at eight loci. Spatial principal component analysis (sPCA) was applied and the frequency maps of the nine alleles which contributed most strongly to sPC1 were examined in detail. By far the greatest part of diversity was summarised by a single spatial principal component (sPC1), oriented along a SouthEast-to-NorthWest axis. The alleles with the top 5% squared loadings were TH01(9.3), D19S433(14), TH01(6), D19S433(15.2), FGA(20), FGA(24), D3S1358(14), FGA(21) and D2S1338(19). These results confirm a clinal pattern over the whole range for at least four loci (TH01, D19S433, FGA, D3S1358). Four of the eight STR loci (or even alleles) considered here can reproducibly capture continental arrangements of diversity. This would, in principle, allow for the exploitation of forensic data to clarify important aspects in the formation of local gene pools.


Efficient synthesis of Man2, Man3, and Man5 oligosaccharides, using mannosyl iodide donors.
[reaction: see text] A highly efficient protocol for making Man(3) and Man(5) oligosaccharides with use of orthogonally protected glycosyl iodide donors has been developed. Glycosylation of a C-2-O-acetyl mannosyl iodide donor in the presence of silver triflate at -40 degrees C initially gave a mixture of the desired alpha-linked mannoside and an orthoacetate resulting from attack at the C-2 acetate. However, upon warming to room temperature the orthoacetate quantitatively rearranged to the desired oligosaccharide. Employing a 3,6-dihydroxy acceptor and subjecting it to double glycosidation quickly afforded high mannose sugars in nearly quantitative yields. Glycosyl iodide donors offer advantages over previously reported chloride donors as the reactions are faster, proceed in higher yields, and are not diminished in higher order constructs. These studies continue to dispel the notion that glycosyl iodides are too reactive to be of synthetic utility.


Before and after wasting disease in common eelgrass Zostera marina along the French Atlantic coasts: a general overview and first accurate mapping.
We examined the original manuscripts of a French national survey conducted in 1933 on the state of common eelgrass Zostera marina beds along the French Atlantic coasts during the period when wasting disease struck the entire North Atlantic population in the 1930s. Based on GIS related techniques and old sets of aerial photographs, we present the first accurate mapping of the Z. marina beds before wasting disease occurred and assess their spatial recolonization since the 1950s in the Chausey Archipelago (France), which contains large Z. marina beds. The national survey confirmed that the Z. marina beds almost totally disappeared from the French coasts during the 1930s. However, the disease symptoms seem to have begun locally a few years before. On the study site, we found that the Z. marina beds were more than twice as extended than as they are today, and covered both subtidal and intertidal areas. By the 1950s, 20 yr after the onset of the disease, the beds had hardly recolonized, and contrary to the recolonization patterns reported elsewhere in Europe, they were mainly restricted to subtidal areas. The subtidal and intertidal Z. marina beds on the site are now rapidly expanding.


Intraindividual Comparison of 99mTc-Methylene Diphosphonate and Prostate-Specific Membrane Antigen Ligand 99mTc-MIP-1427 in Patients with Osseous Metastasized Prostate Cancer.
The objective of this study was to evaluate the rate of detection of bone metastases obtained with the prostate-specific membrane antigen (PSMA)-targeting tracer 99mTc-MIP-1427, as opposed to conventional bone scanning with 99mTc-methylene diphosphonate (99mTc-MDP), in a collective of patients with known advanced-stage osseous metastasized prostate cancer. Methods: Twenty-one patients with known metastatic disease were staged with both conventional bone scanning and PSMA ligand scintigraphy within a time frame of less than 10 d. Imaging included planar whole-body scanning and SPECT or SPECT/CT with 2 bed positions 3 h after injection of either 500-750 MBq of 99mTc-MIP-1427 or 600-750 MBq of 99mTc-MDP. Lesions were scored as typical tumor, equivocal (benign/malignant), or normal within a standard reporting schema divided into defined anatomic regions. Masked and consensus readings were performed with sequential unmasking: planar scans first, then SPECT/CT, the best evaluable comparator (including MRI), PET/CT, and follow-up examinations. Results: Eleven patients had PSMA-positive visceral metastases that were predictably not diagnosed with conventional bone scanning. However, SPECT/CT was required to distinguish between soft-tissue uptake and overlapping bone. Four patients had extensive 99mTc-MDP-negative bone marrow lesions. Seven patients had superscan characteristics on bone scans; in contrast, the extent of red marrow involvement was more evident on PSMA scans. Only 3 patients had equivalent results on bone scans and PSMA scans. In 16 patients, more suspect lesions were detected with PSMA scanning than with bone scanning. In 2 patients (10%), a PSMA-negative tumor phenotype was present. Conclusion: PSMA scanning provided a clear advantage over bone scanning by reducing the number of equivocal findings in most patients. SPECT/CT was pivotal for differentiating bone metastases from extraosseous tumor lesions.


Visceral leishmaniasis in patients with AIDS: report of three cases treated with pentavalent antimony and interferon-gamma.
The optimal therapy for visceral leishmaniasis in patients with AIDS is unknown. We describe herein three patients with advanced AIDS and disseminated leishmaniasis who were treated with meglumine antimoniate plus interferon-gamma. The conditions of the three patients rapidly improved, and the therapeutic combination drastically reduced the parasite burden; after administration of antiprotozoal therapy for 4 weeks, cultures of bone marrow were negative for two of the three patients. Interferon-gamma was well tolerated. Because the patients died of other AIDS-related diseases in the months following therapy, the efficacy of the combination of meglumine antimoniate and interferon-gamma for preventing relapses remains unknown.


Do heat shock proteins play a role in Graves' disease? Heat shock protein-specific T-cells from Graves' disease thyroids do not recognize thyroid epithelial cells.
Thyroid-derived T-cells from patients with Graves' disease were analyzed for their reactivity to recombinant heat shock proteins (hsp) and autologous thyroid epithelial cells (TEC). Five of six uncloned T-cell lines responded to stimulation with recombinant mycobacterial 71-kilodalton (kDa) hsp and cross-reacted with the corresponding amoebial and human proteins. Only one line reacted with recombinant 65-kDa hsp. Thyroid-derived T-cell lines also showed a proliferative response to TEC, which could be increased in four of the lines, when hsp expression was induced in thyroid cells by heat stress before the initiation of coculture. Clonal specificity analysis of thyroid-derived T-cell clones, however, demonstrated that distinct T-cells were responsible for the recognition of recombinant hsp and TEC. None of the clones responsive to recombinant hsp recognized TEC, whereas TEC-responsive clones did not react with recombinant hsp. Interestingly, the response of the majority of TEC-reactive clones could be dramatically increased when heat-shocked TEC were used as stimulator cells. These results suggest that T-cells specific for hsp of the 70- or 60-kDa families do not recognize TEC in the autoimmune thyroid gland. Heat shock-inducible proteins may, however, still play a role in the autoimmune process by facilitating the presentation of thyroid-specific autoantigen(s) to autoreactive T-cells.


Molecular mechanisms of building blocks of life towards medicinal applications.
Membrane and membrane-spanning proteins, and non-coding RNA are biomolecules to play central roles in beginning of life and distinguishing higher-order eukaryotes. We have determined the structures of membrane protein-lipids complexes and non-coding RNA-protein complexes by X-ray crystallography and Cryo-EM single particle analysis, and combined with complementary functional analyses, elucidate their molecular mechanisms at atomic resolutions, to promote creating drugs and medical technologies with two venture companies.


Neurofibromatosis type 1 first presented as hypertensive crisis.
Neurofibromatosis type 1 (NF1) is known to cause vascular complications including stenotic and aneurysmal disease. Here, we report a case of a woman in her early 20s, who presented with unilateral facial nerve palsy and hypertensive crisis, and was later found to have multiple bilateral intrarenal microaneurysms along with classic cutaneous manifestations of NF1. A causal relationship between the pathophysiology of NF1 and the development of renal artery microaneurysm and hypertension is proposed in this case report.


Attraction of Callosobruchus maculatus (F.) (Coleoptera: Bruchidae) to four varieties of Lathyrus sativus L. seed volatiles.
Callosobruchus maculatus (F.) (Coleoptera: Bruchidae) is an important stored grain pest of Lathyrus sativus L. (Leguminosae), commonly known as khesari, in India, Bangladesh and Ethiopia. Volatiles were collected from four varieties, i.e., Bio L 212 Ratan, Nirmal B-1, WBK-14-7 and WBK-13-1 of uninfested khesari seeds, and subsequently identified and quantified by gas chromatography mass spectrometry and gas chromatography flame ionization detector analyses, respectively. A total of 23 volatiles were identified in the four varieties of khesari seeds. In Bio L 212 Ratan and WBK-13-1 seeds, nonanal was the most abundant followed by farnesyl acetone; whereas farnesyl acetone was predominant followed by nonanal in Nirmal B-1 and WBK-14-7 khesari seeds. The olfactory responses of female C. maculatus toward volatile blends from four varieties of khesari seeds, and individual synthetic compounds and their combinations were examined through Y-shaped glass tube olfactometer bioassays. Callosobruchus maculatus showed significant preference for the whole volatile blends from Bio L 212 Ratan seeds compared to whole volatile blends from other three varieties. The insect exhibited attraction to five individual synthetic compounds, 3-octanone, 3-octanol, linalool oxide, 1-octanol and nonanal. A synthetic blend of 448, 390, 1182, 659 and 8114 ng/20 μl methylene chloride of 3-octanone, 3-octanol, linalool oxide, 1-octanol and nonanal, respectively, was most attractive to C. maculatus, and this combination might be used for insect pest management program such as baited traps.


Ancient origins of arthropod moulting pathway components.
Ecdysis (moulting) is the defining character of Ecdysoza (arthropods, nematodes and related phyla). Despite superficial similarities, the signalling cascade underlying moulting differs between Panarthropoda and the remaining ecdysozoans. Here, we reconstruct the evolution of major components of the ecdysis pathway. Its key elements evolved much earlier than previously thought and are present in non-moulting lophotrochozoans and deuterostomes. Eclosion hormone (EH) and bursicon originated prior to the cnidarian-bilaterian split, whereas ecdysis-triggering hormone (ETH) and crustacean cardioactive peptide (CCAP) evolved in the bilaterian last common ancestor (LCA). Identification of EH, CCAP and bursicon in Onychophora and EH, ETH and CCAP in Tardigrada suggests that the pathway was present in the panarthropod LCA. Trunk, an ancient extracellular signalling molecule and a well-established paralog of the insect peptide prothoracicotropic hormone (PTTH), is present in the non-bilaterian ctenophore Mnemiopsis leidyi. This constitutes the first case of a ctenophore signalling peptide with homology to a neuropeptide.


Vitamin A deficiency: effect on retinal structure of the moth Manduca sexta.
Sphingid moths (Manduca sexta) were reared for several generations on an artificial diet deficient in vitamin A and its precursors. Retinal tissue from depleted moths was removed for histological examination. There was extensive histolysis in the retinal epithelium and underlying nervous and connective tissues. This pathology correlated with severe visual impairment, even though normal growth, metamorphosis, and reproduction occurred. In the adult this pathology could be reversed when the larvae were reared only on tobacco (its usual host) or on the artificial diet supplemented with beta-carotene or vitamin A palmitate.


Cytochrome c oxidase does not catalyze the anaerobic reduction of NO.
A possible role of reduced cytochrome c oxidase in the metabolism of nitric oxide (NO) has been examined with amperometric and stopped-flow photometric techniques. Reduced purified cytochrome c oxidase and mitochondria showed no catalytic reaction with NO under anaerobic conditions within more than 30 minutes. Only fast binding of NO to the reduced enzyme in a 1:1 stoichiometric ratio was observed. The NO binding rate was strongly decreased in the presence of 1 mM cyanide. These data indicate that, contrary to previous proposals, cytochrome c oxidase in the absence of oxygen does not contribute to physiological NO metabolism.


Validity and reliability of the gender equity scale in nursing education.
Equity is an emerging issue across all sectors of society, and one of the frequently raised concerns in nursing education is gender inequity. An accurate assessment appears to be a key component in creating an environment of gender equity in nursing education. This study aimed to develop a scale of gender equity in nursing education and establish its validity and reliability. In total, 341 senior nursing students participated in the psychometric evaluation of the Gender Equity Scale in Nursing Education. This psychometric evaluation revealed that the 4-subdomain (personal experience of gender inequity, perceptions of gender roles, gender discrimination, and gender biases in class), 23-item measure possesses both good reliability and validity, as well as a good level of internal consistency. The Gender Equity Scale in Nursing Education was developed as a self-report questionnaire for both female and male students and considers gender role stereotypes, gender-biased educational climates, gender discrimination, and gender inequity in nursing education.


Biomechanics of the foot and ankle during gait.
Running is a very popular activity, whether for competition or fitness. Breakdown injuries related to training errors, shoe wear, or change in intensity are frequently seen by the sports medicine physician. In order to understand and treat the pathologic situation, a fundamental understanding of the biomechanics of walking and running is essential. The treating physician must appreciate the distinct differences between the walking and running gait. These differences transcend a simple increase in speed of gait and include distinct changes in joint range of motion and electromyographic activity. Armed with this knowledge, the physician treating a breakdown injury can work to a solution based on scientific understanding rather than anecdotal information.


Effects of reduced muscle temperature on the oxygen uptake kinetics at the start of exercise.
The purpose of this study was to examine the effects of reduced muscle temperature (Tm) on gas exchange kinetics and haemodynamics at the start of exercise. Six male subjects performed moderate cycle exercise under reduced (C) and normal (N) Tm conditions. Tm and rectal temperature were significantly reduced by immersion in cold water (by 6.6 degrees C and 1.8 degrees C, respectively). The increases in oxygen uptake (Vo2) and oxygen pulse (Vo2/HR) during phase 1 (abrupt increase after the start of exercise) were significantly lower under C than under N. The time constant for O2 under C (36.0 +/- 7.7 (SD)s) was significantly greater than under N (27.5 +/- 4.4 s); however, the time constants of cardiac output under C (38.3 +/- 16.6 s) and N (33.7 +/- 18.5 s) were similar. These results suggest that the slower Vo2 on-response under reduced Tm conditions is caused by decreased O2 extraction in working muscle and/or by impairment of oxidative reactions by reduced muscle temperature.


Immunotherapy and tumor microenvironment.
Recent exciting progress in cancer immunotherapy has ushered in a new era of cancer treatment. Immunotherapy can elicit unprecedented durable responses in advanced cancer patients that are much greater than conventional chemotherapy. However, such responses only occur in a relatively small fraction of patients. A positive response to immunotherapy usually relies on dynamic interactions between tumor cells and immunomodulators inside the tumor microenvironment (TME). Depending on the context of these interactions, the TME may play important roles to either dampen or enhance immune responses. Understanding the interactions between immunotherapy and the TME is not only critical to dissect the mechanisms of action but also important to provide new approaches in improving the efficiency of current immunotherapies. In this review, we will highlight recent work on how the TME can influence the efficacy of immunotherapy as well as how manipulating the TME can improve current immunotherapy regimens in some cases.


Neonatal opsoclonus.
Three cases of opsoclonus in normal neonates are reported. There was no evidence of neuroblastoma, encephalitis, or infantile polymyoclonia. It appears that opsoclonus may occur as a transient phenomenon in healthy infants.


Sample size and correlational inference.
In 4 studies, the authors examined the hypothesis that the structure of the informational environment makes small samples more informative than large ones for drawing inferences about population correlations. The specific purpose of the studies was to test predictions arising from the signal detection simulations of R. B. Anderson, M. E. Doherty, N. D. Berg, and J. C. Friedrich (2005). The results of a simulation study in the present article confirmed and extended previous theoretical claims (R. B. Anderson et al., 2005) that in a yes/no correlation detection task, small-sample advantages should occur but should be restricted to particular decision conditions. In 3 behavioral studies, participants viewed larger or smaller samples of data pairs and judged whether each sample had been drawn from a population characterized by a zero correlation or from one characterized by a greater-than-zero correlation. Consistent with traditional statistical theory, accuracy tended to be greater for larger than for smaller samples, though there was a small-sample advantage in 1 experimental condition. The results are discussed in relation to alternative theoretical and behavioral paradigms such as those of Y. Kareev (e.g., 2005) and K. Fiedler and Y. Kareev (2006).


Analyses of L-Type Corner Joints Connected with Auxetic Dowels for Case Furniture.
Tests were carried out to develop and manufacture various types of auxetic dowels using 3D printing technology. These dowels were then used to connect L-type corner joint specimens for case furniture, and their strength and stiffness were analyzed through experimental, theoretical, and numerical means. In the scope of the study, eight different types of auxetic dowels including two inclusion types, two inclusion sizes, and two dowel hole diameters, as well as a reference non-auxetic dowel, were designed. Accordingly, a total of 180 specimens that included 10 replications for each group were tested; 90 were tested under tension and the remaining 90 were tested under compression. The results demonstrated that the assembly force required for the corner joints connected with auxetic dowels was significantly lower compared to non-auxetic dowels. Furthermore, the numerical and theoretical analyses yielded similar outcomes in this study. Both analyses revealed that the dowels used to connect the corner joints experienced substantial stresses during mounting and bending, ultimately leading to their failure. Upon concluding the test results, it was observed that the corner joints connected with dowels featuring rectangular inclusions exhibited superior performance when compared to those with triangular inclusions. In light of these findings, it can be concluded that further enhancements are necessary for auxetic dowels with rectangular inclusions before they can be utilized as alternative fasteners for traditional dowels.


The value and cost effectiveness of abdominal roentgenograms in the evaluation of stab wounds to the abdomen.
The value of roentgenograms of the abdomen in the evaluation and management of stab wounds to the abdomen has not been well documented. This retrospective study demonstrates that the overwhelming majority of patients with injury requiring repair have normal roentgenograms. We also found that, even when abnormal, abdominal roentgenograms make a negligible contribution to the evaluation in these patients. These findings indicate that abdominal roentgenograms are not cost effective in patients with stab wounds to the abdomen and should not be obtained on a routine basis.


Inducible and brain region-specific CREB transgenic mice.
To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different lines of bitransgenic mice, and CREB expression was blocked by addition of doxycycline, an analog of tetracycline. Overexpression of CREB influenced the expression of other members of the CREB/ATF family of transcription factors, consistent with previous reports. In addition, psychostimulant induction of dynorphin, a neuropeptide regulated by drugs of abuse, was up-regulated in striatum. Finally, there was a significant reduction in cocaine-induced locomotor activity in the CREB bitransgenic mice. These results are consistent with a role for CREB in mediating adaptive changes that occur in response to drugs of abuse.


Spinal Cord Stimulation and Related Health Information on Social Media: An Analysis of Instagram Posts.
Spinal cord stimulation (SCS) has been a well-established, effective, minimally invasive procedure for the treatment of chronic medically refractory neuropathic pain involving the limbs and trunk. Social media platforms, including Instagram, are increasingly being used for medical education and sharing patient experiences. This study aimed to investigate posts related to SCS on Instagram. This study presents a comprehensive analysis of Instagram posts utilizing the hashtags #spinalcordneuromodulation, #spinalcordstimulation, #spinalcordstimulationsurgery, #spinalcordstimulationtherapy, and #spinalcordstimulationimplant, all of which were collected on August 1, 2023. The outcomes were organized into four distinct source-based categories: posts generated by medical practitioners (both surgeons and non-surgeons); content shared by medical organizations; content created by patients; and content from indeterminate categories. The content was further classified based on its nature, encompassing educational material and reflections on patient or physician experiences. Moreover, the impact of users was evaluated in terms of their follower count and the count of posts. The search yielded a total of 4983 posts. The majority of posts were created by medical practitioners (38.53%, n = 1920). The distribution of remaining Instagram posts about SCS was as follows: medical organizations for 35% (n = 1744), patients for 24.12% (n = 1202), and indeterminate categories for 2.35% (n = 117). Among the collected posts, 348 (41.4%) originated from accounts associated with medical practitioners, 286 (34%) from medical organizations, 145 (17.2%) from patients, and 62 (7.4%) remained unspecified. The statistical analysis revealed a significant difference in follower distribution between medical practitioners and all other groups (p<0.001). Reported side effects included pain over the implant (n = 257; 88.92%), lead migration (n = 18; 6.22%), infection (n = 9; 3; 11%), and seroma (n = 5; 1.73%). When searching for posts about SCS on Instagram, one is more likely to encounter posts authored by medical practitioners that are mostly focused on educational content. Posts created by medical practitioners may be overshadowed and buried among numerous other posts created by patients. We suggest posting educational medical content with the hashtag #MedEd in an attempt to make educational content more easily accessible.


Glutathione S-transferase mu1 deficiency, cigarette smoking and coronary artery disease.
While genetic variation accounts for a large proportion of interindividual differences in coronary artery disease (CAD) development, environmental factors such as cigarette smoking may genotype-dependently initiate or accelerate the risk. Glutathione S-transferase mu1 (GSTM1) is one of the GST isoenzymes and contributes to the detoxification process of organic compounds produced by cigarette smoking. In the present study we explored the hypothesis that GSTM1 deficiency, caused by GSTM1 null allele, may predispose subjects to cigarette smoking related CAD risk. Cross-sectional. We genotyped the GSTM1 null allele in 868 angiographically characterized CAD patients who were consecutively recruited in the present study. The frequency of the null genotype in this high-risk patient population was 57.1% (55.4% for males and 61.0% for females). While 75.7% male and 50.7% female null GSTM1 patients had significant CAD as defined by one or more significantly stenosed coronary arteries, 79.3% male and 48.3% female patients with positive GSTM1 also had the significant CAD (P > 0.05). However, although 54.3% male and 55.2% female GSTM1 null patients had triple vessel disease, only 45.7% male and 44.5% female GSTM1 positive patients had the severe disease. Controlling for cigarette smoking did not change the relationship. The occurrences of MI were 37.9% in male and 31.4% in female with the null genotype whereas they were 42.8% in male 37.6% in female with positive GSTM1 (P > 0.05). Using logistic regression analyses, we found no interactions between GSTM1 genotype and cigarette smoking in relation to CAD or MI. While our data may be consistent with that the GSTM1 null genotype predisposes subjects to cigarette smoking related severe CAD, interactive effect on CAD risk is minor and insignificant. GSTM1 deficiency alone is not sufficient to cause CAD.


Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma.
Mitochondrial DNA (mtDNA) mutations and deletions are frequently observed in cancer, and contribute to altered energy metabolism, increased reactive oxygen species (ROS), and attenuated apoptotic response to anticancer agents. The mechanisms by which cells maintain mitochondrial genomic integrity and the reason why cancer cells exhibit more frequent mtDNA mutations remain unclear. Here, we report that the tumor suppressor molecule p53 has a novel role in maintaining mitochondrial genetic stability through its ability to translocate to mitochondria and interact with mtDNA polymerase gamma (pol gamma) in response to mtDNA damage induced by exogenous and endogenous insults including ROS. The p53 protein physically interacts with mtDNA and pol gamma, and enhances the DNA replication function of pol gamma. Loss of p53 results in a significant increase in mtDNA vulnerability to damage, leading to increased frequency of in vivo mtDNA mutations, which are reversed by stable transfection of wild-type p53. This study provides a mechanistic explanation for the accelerating genetic instability and increased ROS stress in cancer cells associated with loss of p53.


The Affective Neuroscience of Aging.
Although aging is associated with clear declines in physical and cognitive processes, emotional functioning fares relatively well. Consistent with this behavioral profile, two core emotional brain regions, the amygdala and ventromedial prefrontal cortex, show little structural and functional decline in aging, compared with other regions. However, emotional processes depend on interacting systems of neurotransmitters and brain regions that go beyond these structures. This review examines how age-related brain changes influence processes such as attending to and remembering emotional stimuli, regulating emotion, and recognizing emotional expressions, as well as empathy, risk taking, impulsivity, behavior change, and attentional focus.


Explaining and avoiding failure modes in goal-directed generation of small molecules.
Despite growing interest and success in automated in-silico molecular design, questions remain regarding the ability of goal-directed generation algorithms to perform unbiased exploration of novel chemical spaces. A specific phenomenon has recently been highlighted: goal-directed generation guided with machine learning models produce molecules with high scores according to the optimization model, but low scores according to control models, even when trained on the same data distribution and the same target. In this work, we show that this worrisome behavior is actually due to issues with the predictive models and not the goal-directed generation algorithms. We show that with appropriate predictive models, this issue can be resolved, and molecules generated have high scores according to both the optimization and the control models.


Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile Derivatives as Anticancer Agents.
Herein, we report an environmentally friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives. The in-vitro anticancer activities of these compounds were evaluated against four human tumor cell lines. Among all the synthesized derivatives, compound 4i, which has substituent 3-hydroxy-4-methoxyphenyl is found to have the highest GI50 value of 32.7 μM, 55.3 μM, 34.3 μM, 28.9 μM for MCF-7, K562, HeLa and PC-3 cancer cell lines respectively. A docking study of the newly synthesized compounds were performed, and the results showed good binding mode in the active site of thymidylate synthase enzyme. ADME properties of synthesized compounds were also studied and showed good drug like properties.


An exploration of female genital mutilation.
Female genital mutilation (FGM) is a form of violence against women that has recently been labeled a public health issue. This article will define and describe the procedure as well as discuss its physical and psychological implications. An exploration of the cultural significance of the practice will shed light on its continued existence in underdeveloped and developed nations. In addition, an examination of suggested guidelines for creating and implementing effective interventions will ensue.


Multimodal Local Resonators for Low-Frequency Amelioration of Acoustic Black Holes.
Acoustic black holes (ABHs) are effective at suppressing vibrations at high frequencies, but their performance at low frequencies is limited. This paper aims to improve the low-frequency performance of ABH plates through the design of a metamaterial acoustic black hole (MMABH) plate. The MMABH plate consists of a double-layer ABH plate with a set of periodic local resonators installed between the layers. The resonators are tuned to the low-frequency peak points of the ABH plate, which are identified using finite element analysis. To dissipate vibration energy, the beams of the resonators are covered with damping layers. A modal analysis of the MMABH plate is performed, confirming its damping effect over a wide frequency band, especially at low frequencies.


Relationship between the intake of energy and basic nutrients and the BMI values in group of children aged 10-12.
According to the WHO data in January 2007, 14 million children were overweight in the countries of the European Union. The problem of childhood obesity should be considered as one of the biggest challenges facing twenty- first century nutrition and pediatrics. The aim of this study was to show the correlation between energy, basic nutrients intake and BMI of school children aged 10-12 years, using Pearson's correlation coefficient. 169 pupils (69 from Krakow and 100 from Skawina), aged 10-12, participated in these studies. The studies were approved by the Board of Education, school principals and the parents. On the basis of measurements of weight and height, body mass index (BMI) was calculated. 24 h dietary recalls were collected in the spring and autumn of 2006, for 4 selected days per week. Intake of energy, total carbohydrate and fat did not met requirements, but intake of protein was too high. Proper weight, based on BMI values in the population aged 10-12, were found in 74.9% of boys and 81.2% of girls. Deficiencies in body weight occurred in 4.2% and 3.4%, overweight in 15.6% and 10.0% while obesity in 5.3% and 5.4% of respondents. Inverse correlation was found between the implementation of standards for energy and BMI values of children. It was observed positive correlation between the consumption of total and animal protein and BMI value. children, underweight, obesity, BMI, nutrients, nutrition, Pearson's correlation coefficient.


Emotion regulation deficits in regular marijuana users.
Effective regulation of negative affective states has been associated with mental health. Impaired regulation of negative affect represents a risk factor for dysfunctional coping mechanisms such as drug use and thus could contribute to the initiation and development of problematic substance use. This study investigated behavioral and neural indices of emotion regulation in regular marijuana users (n = 23) and demographically matched nonusing controls (n = 20) by means of an fMRI cognitive emotion regulation (reappraisal) paradigm. Relative to nonusing controls, marijuana users demonstrated increased neural activity in a bilateral frontal network comprising precentral, middle cingulate, and supplementary motor regions during reappraisal of negative affect (P < 0.05, FWE) and impaired emotion regulation success on the behavioral level (P < 0.05). Amygdala-focused analyses further revealed impaired amygdala downregulation in the context of decreased amygdala-dorsolateral prefrontal cortex functional connectivity (P < 0.05, FWE) during reappraisal in marijuana users relative to controls. Together, the present findings could reflect an unsuccessful attempt of compensatory recruitment of additional neural resources in the context of disrupted amygdala-prefrontal interaction during volitional emotion regulation in marijuana users. As such, impaired volitional regulation of negative affect might represent a consequence of, or risk factor for, regular marijuana use. Hum Brain Mapp 38:4270-4279, 2017. © 2017 Wiley Periodicals, Inc.


Modeling of Solid-Liquid Equilibria in Deep Eutectic Solvents: A Parameter Study.
Deep eutectic solvents (DESs) are potential alternatives to many conventional solvents in process applications. Knowledge and understanding of solid-liquid equilibria (SLE) are essential to characterize, design, and select a DES for a specific application. The present study highlights the main aspects that should be taken into account to yield better modeling, prediction, and understanding of SLE in DESs. The work is a comprehensive study of the parameters required for thermodynamic modeling of SLE-i.e., the melting properties of pure DES constituents and their activity coefficients in the liquid phase. The study is carried out for a hypothetical binary mixture as well as for selected real DESs. It was found that the deepest eutectic temperature is possible for components with low melting enthalpies and strong negative deviations from ideality in the liquid phase. In fact, changing the melting enthalpy value of a component means a change in the difference between solid and liquid reference state chemical potentials which results in different values of activity coefficients, leading to different interpretations and even misinterpretations of interactions in the liquid phase. Therefore, along with reliable modeling of liquid phase non-ideality in DESs, accurate estimation of the melting properties of their pure constituents is of clear significance in understanding their SLE behavior and for designing new DES systems.


Single dose of tiotropium improves the 6-minute walk distance in chronic obstructive pulmonary disease.
The aim of this study was to evaluate the effect of a single dose of tiotropium on the exercise capacity of stable chronic obstructive pulmonary disease (COPD) patients. The study was a randomized, placebo-controlled, double-blind, cross-over study. Forty-four stable COPD patients with moderate to severe airway obstruction were selected according to the GOLD criteria. The regular anticholinergic therapies of the patients were interrupted one week before the test. In the morning hours of the first day, half the group was given one capsule (18 mcg) of tiotropium and the other half was given placebo as inhalation using the HandiHaler device. Before and 120 min after the medication, the 6-min walk test was performed. Oxygen saturation, modified Borg dyspnea ratings, blood pressure, and heart rate were recorded before and after the test. The same procedure was repeated at the same time on the third day but this time the patients were given placebo if they used tiotropium on the first day and vice versa. Before using tiotropium or placebo there was no difference between 6-min walk distances. The 6-min walk distance after the use of tiotropium (429.3 +/- 70.6 m) was significantly longer than that after the use of placebo (414.7 +/- 74.6 m). The changes in Borg dyspnea ratings and arterial oxygen saturation values with tiotropium and placebo use were not significant. We conclude that exercise capacity might be improved by using a single-dose tiotropium inhalation in moderate to severe COPD patients.


Imipramine induces alterations in proenkephalin and prodynorphin mRNAs level in the nucleus accumbens and striatum in the rat.
Endogenous opioids have been implicated in the mechanism of action of antidepressant drugs. In this study, we evaluated effects of single and repeated imipramine administration on proenkephalin and prodynorphin gene expression in the rat nucleus accumbens and striatum. In situ hybridization study showed that single imipramine injection (10 mg/kg, i.p.) decreased the level of proenkephalin (by ca. 20%) and prodynorphin (by ca. 25%) mRNA to the same extent in both structures. Repeated imipramine administration (10 mg/kg i.p. twice daily for 10 days) had no effect on proenkephalin mRNA level, whereas the prodynorphin gene expression was regulated differently. At 3 h after the last dose of imipramine the prodynorphin mRNA level was decreased (by ca. 25%) in the striatum, but not in the nucleus accumbens, whereas at 24 h an up-regulation (by ca. 27%) of prodynorphin mRNA level could be observed in the nucleus accumbens only. In the light of involvement of opioids in mood regulation, these adaptive changes may participate in neurochemical mechanisms of antidepressant therapy.


Patients who present to the emergency department and leave without being seen: prevalence, predictors and outcomes.
To identify the prevalence, predictors and outcomes of patients who leave without being seen (LWBS) in one hospital emergency department (ED). A descriptive, retrospective cohort study design was used. Data were extracted from the ED Information System. Multivariate logistic regression identified independent predictors of patients who LWBS. Two main outcomes were studied: the proportion of patients who waited longer than recommended and the proportion of patients who represented to the ED within 72 h. A large regional teaching hospital ED in South East Queensland, Australia. A total of 64 292 patient presentations made to the ED from 9 August 2008 to 8 August 2009. The prevalence of patients who LWBS was 10.7%. Independent predictors of LWBS included younger age, lower urgency triage category allocation, arrival by means other than ambulance, evening and night shift presentations, winter season, weekend presentations and presenting complaint category of 'gastrointestinal' or 'paediatric'. When compared with patients who waited, those who LWBS comprised higher proportions of waiting longer than recommended (LWBS: 77.2% vs. waited: 52.0%, P<0.001) and higher proportions of representations to ED within 72 h (LWBS: 10.3% vs. waited: 5.4%, P<0.001). Outcomes investigated in this study indicate that room for improvement exists not only for patients who LWBS but all patients presenting to the ED. The most powerful predictors of LWBS were lower urgency triage allocation and evening and night shift presentations. This suggests that service improvements could be targeted during 'out of business hours' for those with less emergent conditions.


Vasopressin in cardiovascular patients: therapeutic implications.
Vasopressin is a vital homeostatic protein which regulates fluid balance via its antidiuretic effects and vascular tone via its vasoconstrictive effects. Endogenous vasopressin deficiency has been implicated in several disease states resulting in vasodilatory shock. In particular, vasopressin levels are low in patients following cardiac surgery and in those with ventricular dysrhythmias. Several recent studies have demonstrated the effectiveness of exogenous vasopressin in providing haemodynamic support in patients with postcardiopulmonary bypass vasodilatory shock and refractory ventricular fibrillation. This manuscript reviews the pathophysiological and clinical basis for vasopressin replacement in patients with cardiovascular collapse.


Regulation of skeletal muscle glycogenolysis during exercise.
Muscle-glycogen breakdown during exercise is influenced by both local and systemic factors. Contractions per se increase glycogenolysis via a calcium-induced, transient increase in the activity of phosphorylase a, and probably also via increased concentrations of Pi. In fast-twitch muscle, increases in the AMP and IMP levels may increase phosphorylase activity. The rate of muscle-glycogen breakdown during exercise depends on the pre-exercise glycogen concentration and is also influenced by hormones. Insulin may inhibit glycogen breakdown, whereas epinephrine enhances the rate of glycogen use in contracting muscle by increasing the phosphorylase a activity via increased cyclic AMP production. The availability of blood-borne substrates may also influence muscle glycogenolysis and, therefore, exercise performance.


High Resolution Imaging of DNA Methylation Dynamics using a Zebrafish Reporter.
As one of the major epigenetic modifications, DNA methylation is constantly regulated during embryonic development, cell lineage commitment, and pathological processes. To facilitate real-time observation of DNA methylation, we generated a transgenic zebrafish reporter of DNA methylation (zebraRDM) via knockin of an mCherry-fused methyl-CpG binding domain (MBD) probe driven by the bactin2 promoter. The probe colocalized with heterochromatin, and its intensity was positively correlated with 5 mC immunostaining at a subcellular resolution in early embryos. Biochemical assays indicated that cells with stronger fluorescence maintained a higher level of DNA methylation, and time-lapse imaging at the blastula stage showed that the level of DNA methylation was transiently strengthened during mitosis. By crossing zebraRDM with other fluorescent transgenic lines, we demonstrate that the reporter can visually distinguish different cell lineages in organs like the heart. Our zebraRDM reporter therefore serves as a convenient and powerful tool for high-resolution investigation of methylation dynamics in live animals.


Impact of Oral Sensory Motor Stimulation on Feeding Performance, Length of Hospital Stay, and Weight Gain of Preterm Infants in NICU.
One of the limiting factors for early hospital discharge in preterm infants is their inability to feed sufficiently to obtain consistent weight gain. Therefore, feeding difficulty is one of the most significant issues with which a preterm infant is faced. The purpose of this study was to examine the effect of oral sensory motor stimulation on feeding performance, length of hospital stay, and weight gain in preterm infants at 30 - 32 weeks of gestational age. Premature infants (n = 20) were randomly assigned to experimental and control groups. The experimental group received oral sensory motor stimulation of the oral structures (15 minutes / day) for 10 successive days, while these stimulations were not offered to the control group. Days elapsed to achieve oral feeding, length of hospital stay, and weight gain in the two groups were assessed. Transition to oral feeding was acquired significantly earlier in the infants in the experimental group than in the controls: 13 and 26 days, respectively (P < 0.001). Likewise, the length of hospitalization was significantly shorter in the experimental group than in the control group: 32 days and 38 days, correspondingly (P < 0.05). The two groups showed no significant difference in terms of weight gain in the first, second, third, and fourth weeks of birth: first week: 100 vs. 110; second week: 99 vs. 111; third week: 120 vs. 135; and fourth week: 129 vs. 140. The present research revealed that the number of days to reach oral feeding in our preterm babies was decreased by oral motor stimulation, which in turn conferred earlier hospital discharge.


Enoxaparin in acute coronary syndromes: evidence for superiority over placebo or untreated control.
Heparins, both standard unfractionated heparin (SUFH) and low-molecular weight heparin, play a prominent role in the treatment of acute coronary syndromes. Enoxaparin has been shown in 2 trials to be superior to heparin but has not been compared with placebo or untreated control. A putative enoxaparin versus placebo/control odds ratio (OR) was computed with a recently described statistical technique with the logarithm of the ORs of the pooled results of both the enoxaparin-SUFH trials and SUFH-placebo or controlled trials. The combined heparin versus control results show a 33% reduction in the risk of death or acute myocardial infarction (AMI), with an OR of 0.67 (95% confidence interval [CI], 0.45 to 0.99). At up to 12 weeks (data from only 4 trials), the combined results show a 21% reduction (OR, 0.79; 95% CI, 0.54 to 1.15; P =.23). The 2 enoxaparin trials show a nonsignificant 20% reduction in the risk of death or AMI during treatment (OR, 0.80; 95% CI, 0.68 to 1.16; P =.24) and a significant reduction at 43 days (OR, 0.82; 95% CI, 0.69 to 0.97; P =.022). With these pooled data, the putative OR for enoxaparin versus placebo/untreated control during treatment is 0.53 (95% CI, 0.31 to 0.92; P =.023). The data are consistent with a 47% reduction in the risk of death or AMI. The difference persists on longer term follow-up period (OR, 0.65; 95% CI, 0.43 to 0.98; P =.04). The risk of bleeding is nonsignificantly increased (OR, 2.32; 95% CI, 0.8 to 7.85; P =.51). On the basis of this methodology, enoxaparin would appear to be more effective than placebo when added to aspirin in acute coronary syndromes. Moreover, the effect of enoxaparin is similar to the results of a metaanalysis of trials of other low-molecular weight heparins versus placebo/control.


Gynecological and obstetrical aspects of Enterobius vermicularis infection.
Enterobiasis is an easily recognizable and treatable disease with higher incidence among children. Based on these facts, its clinical importance is usually underestimated. This infection also occurs during adulthood and without treatment, it can cause severe complications in some rare cases. Unnoticed subclinical infection in women can lead to infertility and even to life-threatening conditions. It is also emphasized in this paper that the treatment of identified enterobiasis during pregnancy needs caution. After reviewing the current scientific literature, two gynecological cases are presented here.


[Bone tissue regeneration using stem cells].
In vitro modification of mesenchymal stem cells and materials via tissue engineering is useful for bone regeneration. In this paper, we briefly summarize our bone tissue engineering approach. It is also known that RNA interference (RNAi) can regulate cell proliferation as well as differentiation cascade. Recently, our study using siRNA demonstrated that bone matrix formation by osteoblastic cells can be inhibited by certain types of siRNA. These findings can show that the proliferation/differentiation of the cells used in regenerative medicine could be regulated by siRNA.


Intracellular calcium affects neutrophil chemoattractant expression by macrophages in rats with cerulein-induced pancreatitis.
Pancreatitis complicated with infection often results in the development of multiple organ failure. We investigated the role of altered intracellular calcium as a priming signal for cytokine-induced neutrophil chemoattractant expression in this process. Agents modulating cytosolic Ca2+ were utilized to study the in vivo and in vitro cytokine-induced neutrophil chemoattractant expression for macrophages in rats with cerulein-induced pancreatitis after intraperitoneal administration of lipopolysaccharide as a septic challenge. Pretreatment with the calcium channel blocker verapamil significantly reduced serum cytokine-induced neutrophil chemoattractant concentrations in rats with cerulein-induced pancreatitis after septic challenge. Lipopolysaccharide-stimulated in vitro cytokine-induced neutrophil chemoattractant (CINC) production by peritoneal macrophages was significantly enhanced by pretreatment with thapsigargin (an inhibitor of the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187 (a calcium-specific ionophore, extracellular Ca2+ influx). Pretreatment with U73122 (a phospholipase C inhibitor) inhibited lipopolysaccharide-stimulated but not basal cytokine-induced neutrophil chemoattractant production, while verapamil (a calcium channel blocker), TMB-8 (an inhibitor of calcium release from endoplasmic reticulum), and W7 (calmodulin antagonist) completely abrogated the chemoattractant production. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of macrophages to release cytokine-induced neutrophil chemoattractant following triggering with lipopolysaccharide during acute cerulein pancreatitis.


Seasonal recruitment and survival strategies of Palisada cervicornis comb. nov. (Ceramiales, Rhodophyta) in coral reefs.
As marine tropical ecosystems deteriorate and lose biodiversity, their communities are shifting to being dominated by a few species, altering ecosystem's functioning and services. Macroalgae are becoming dominant on coral reefs, and are frequently observed outcompeting corals. Turf algal assemblages are the base of energy flow in these systems and one of the most abundant types of macroalgae on coral reefs, but little is known about their biology and diversity. Through molecular and morphological analyses, we identified the turf-forming species Laurencia cervicornis, and by studying seasonal recruitment and the impact of herbivorous fishes on its abundance, we describe its survival strategy. The molecular analyses used a total of 45 rbcL gene sequences including eight current genera within the Laurencia complex and two new sequences of L. cervicornis and strongly support the new combination of Palisada cervicornis comb. nov. In addition, a detailed morphological characterization including the description of reproductive structures is provided. Palisada cervicornis was seen recruiting in all seasons but was typically in low abundance. Specimens grown on tiles in fish exclosure cages were devoured in less than 4 h when offered to fishes. Even though many species of the Laurencia complex have chemicals that deter herbivory, species within the genus Palisada lack feeding deterrents and thus are highly palatable. We suggest that P. cervicornis is a palatable species that seems to survive in the community by obtaining a size-refuge from herbivory within turf communities.


Studies on the "signal" constituents for the evaluation of animal crude drugs. III. Nucleic acid components.
An analytical method for determining the contents of 7 nucleic acid bases, 6 ribonucleosides and 5 deoxyribonucleosides in animal crude drugs were established. The contents in free nucleic acid components (the ice-cold extracts) and in total nucleic acid components (the heated extracts) of 8 crude drugs were quite different from one another, indicating that these content patterns could be used as a "signal" of each animal crude drug. For example, the contents of inosine in Lumbricus, uracil in Cervi Parvum Cornu, and guanine and hypoxanthine in Hippocampus were high. The total contents in each crude drug were about twice or three times as large as the free contents. The main degradation products by the heated extracts were adenine and guanine. These results suggested that the contents of nucleic acid components could be one of the "signal" constituents for evaluation of animal crude drugs.


[Mental impairment in children with cerebral palsy: diagnosis and treatment].
The article covers the problems of diagnosis and treatment of mental impairment in children with cerebral palsy. Mental disorders in cerebral palsy include cognitive impairment (disorders of perception, memory, attention, motor-visual coordination, intelligence and speech), border disorders (cerebral/asthenic, neurosis-like, psychopathic-like syndromes) and personality disorders (accentuation of character, mental infantilism). Diagnosis of mental disorders in patients with cerebral palsy is a challenging task, due to various combinations of them with physical, speech and sensory disorders, which requires a differentiated approach. Current trends in comprehensive system of rehabilitation, including medical and social, and psychological-pedagogical correction of cognitive, emotional and behavioral disorders, in cerebral palsy are reviewed. Experience of using cortexin, which compensates for cognitive impairment and improves social adaptation, is discussed.


When Teamwork Works: Examining the Relationship Between Leader-Member Exchange Differentiation and Team Creativity.
Drawing on team creativity literature and social comparison theory, we investigate how leader-member exchange (LMX) differentiation influences team creativity. Using a survey based on 91 R&D teams from Chinese companies, we observe that LMX differentiation is negatively related to team creativity (β = -0.35, p < 0.01). More importantly, we demonstrate that team behavioral integration mediates the relationship between LMX differentiation and team creativity (indirect effect size = -0.72, with 95% CI of -1.91, -0.13), and team emotional intelligence (TEI) moderates the relationship between LMX differentiation and team behavioral integration (β = 0.23, p < 0.05), such that LMX differentiation has a weaker negative influence on team behavioral integration when TEI is higher. These results provide relevant suggestions for organizational team building, management, and development.


Immunotherapy targeting toll-like receptor 2 alleviates neurodegeneration in models of synucleinopathy by modulating α-synuclein transmission and neuroinflammation.
Synucleinopathies of the aging population are an heterogeneous group of neurological disorders that includes Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and are characterized by the progressive accumulation of α-synuclein in neuronal and glial cells. Toll-like receptor 2 (TLR2), a pattern recognition immune receptor, has been implicated in the pathogenesis of synucleinopathies because TLR2 is elevated in the brains of patients with PD and TLR2 is a mediator of the neurotoxic and pro-inflammatory effects of extracellular α-synuclein aggregates. Therefore, blocking TLR2 might alleviate α-synuclein pathological and functional effects. For this purpose, herein, we targeted TLR2 using a functional inhibitory antibody (anti-TLR2). Two different human α-synuclein overexpressing transgenic mice were used in this study. α-synuclein low expresser mouse (α-syn-tg, under the PDGFβ promoter, D line) was stereotaxically injected with TLR2 overexpressing lentivirus to demonstrate that increment of TLR2 expression triggers neurotoxicity and neuroinflammation. α-synuclein high expresser mouse (α-Syn-tg; under mThy1 promoter, Line 61) was administrated with anti-TLR2 to examine that functional inhibition of TLR2 ameliorates neuropathology and behavioral defect in the synucleinopathy animal model. In vitro α-synuclein transmission live cell monitoring system was used to evaluate the role of TLR2 in α-synuclein cell-to-cell transmission. We demonstrated that administration of anti-TLR2 alleviated α-synuclein accumulation in neuronal and astroglial cells, neuroinflammation, neurodegeneration, and behavioral deficits in an α-synuclein tg mouse model of PD/DLB. Moreover, in vitro studies with neuronal and astroglial cells showed that the neuroprotective effects of anti-TLR2 antibody were mediated by blocking the neuron-to-neuron and neuron-to-astrocyte α-synuclein transmission which otherwise promotes NFκB dependent pro-inflammatory responses. This study proposes TLR2 immunotherapy as a novel therapeutic strategy for synucleinopathies of the aging population.


Clinical significance of serum vascular endothelial growth factor and complement 3a levels in patients with colorectal cancer in southern Iran.
Colon cancer (CRC) is perhaps the second most common cause of cancer mortality. This study determined the clinical significance of serum vascular endothelial growth factor (VEGF) and serum complement 3a (C3a) levels in patients with CRC in Fars province, southern Iran. Between June 2010 and June 2012, 110 patients with CRC of both genders and different age groups were divided into 3 groups. Group A included patients who had just undergone surgery; Group B had undergone chemotherapy after surgery; and Group C had undergone chemotherapy and radiotherapy after surgery. Twenty one healthy subjects with normal colonoscopy were considered as a control group. ELISA was undertaken to determine VEGF and C3a levels before and after treatment measures. The mean age of patients was 53.9±14.1 years. Considering VEGF level, a significant decrease was visible after treatment measures in groups A and B, but not Group C. For VEGF level, the difference was not statistically significant between two genders and various age groups before and after treatment. No significant difference was found for VEGF level between patients and normal group before any treatment. Regarding C3a levels in 101 subjects, they significantly decreased after treatment measures. Before and after treatment, the difference was statistically significant between two genders, but was not statistically significant among various age groups. As VEGF and C3a levels were significantly lower in patients after treatment, these may be beneficial markers in assessment of CRC therapy especially in early stages.


The cleavage pattern of calanoid copepods-a case study.
Many crustacean groups show stereotyped cleavage patterns during early ontogeny. However, these patterns differ between the various major crustacean taxa, and a general mode is difficult to extract. Previous studies suggested that also copepods undergo an early cleavage with a more or less stereotyped pattern of blastomere divisions and fates. Yet, copepod embryology has been largely neglected. The last investigation of this kind dates back more than a century and the results are somewhat contradictory when compared with those of other researchers. To overcome these problems, we studied the early development of a so far undescribed calanoid copepod species, Skistodiaptomus sp., applying histochemical staining, confocal laser scanning microscopy, and bifocal 4D microscopy. The blastomere arrangement of the four-cell stage of this species varies to a large degree. It can either form a typical radial pattern with the four blastomeres lying in one plane or a tilted orientation of the axes connecting the sister cells of the previous division. In both cases, a stereotyped division pattern is maintained inside each quadrant during subsequent cleavages. In addition, we found two types of blastomere arrangements with a mirror symmetry. Most divisions within the quadrants follow the perpendicularity rule until the eighth cleavage. Deviations from this rule occur only in the narrow regions where the different quadrants touch and near the site of gastrulation. Gastrulation is initiated around the descendants of one individually identifiable blastomere of the 16-cell stage. This cell divides in a specific manner forming a characteristic cell arrangement, the gastrulation triangle. This gastrulation triangle initiates the internalization process of the gastrulation and it is encircled by another characteristic cell type, the crown cells. Our observations reveal several similarities to the early development of Calanus finmarchicus, another calanoid species. These relate to blastomere arrangements and divisions and the pattern of gastrulation. As Calanoida represent a basal or near basal branch of the copepod tree, this description will provide the ground for reconstruction of the cleavage pattern of the last common ancestor of Copepoda.


Regulation of astrocyte activity and immune response on graphene oxide-coated titanium by electrophoretic deposition.
Introduction: Astrocytes play crucial role in modulating immune response in the damaged central nervous system. Numerous studies have investigated the relationship between immune responses in astrocytes and brain diseases. However, the potential application of nanomaterials for alleviating neuroinflammation induced by astrocytes remains unexplored. Method: In this study, we utilized electrophoretic deposition (EPD) to coat graphene oxide (GO) onto titanium (Ti) to enhance the bioactivity of Ti. Results: We confirmed that GO-Ti could improve cell adhesion and proliferation of astrocytes with upregulated integrins and glial fibrillary acidic protein (GFAP) expression. Moreover, we observed that astrocytes on GO-Ti exhibited a heightened immune response when exposed to lipopolysaccharide (LPS). Although pro-inflammatory cytokines increased, anti-inflammatory cytokines and brain-derived neurotrophic factors involved in neuroprotective effects were also augmented through nuclear localization of the yes-associated protein (YAP) and nuclear factor kappa B (NF-κB). Discussion: Taken together, GO-Ti could enhance the neuroprotective function of astrocytes by upregulating the expression of anti-inflammatory cytokines and neuroprotective factors with improved cell adhesion and viability. Consequently, our findings suggest that GO-Ti has the potential to induce neuroprotective effects by regulating cell activity.


The interaction between aggrecan gene VNTR polymorphism and cigarette smoking in predicting incident symptomatic intervertebral disc degeneration.
An association between the aggrecan variable number of tandem repeat (VNTR) polymorphism and the disc degeneration has been previously reported in Finnish men, and smoking had previously been suspected of causing disc degeneration. However, the interaction between aggrecan gene VNTR polymorphism and smoking in symptomatic intervertebral disc degeneration (IDD) has not been well studied. To examine the interaction between aggrecan gene VNTR and smoking in the susceptibility of symptomatic IDD of Chinese Han in northern China, intervertebral discs of 132 participants were evaluated on magnetic resonance imaging, using decreased signal intensity. After harvesting the blood samples, the aggrecan gene VNTR region was analyzed using polymerase chain reaction (PCR). The data indicated that between the two groups, participants carrying one or two alleles ≤25 repeats who did not smoke showed a 1.102-fold increased risk for symptomatic IDD (p= 0.855; 95% confidence interval 0.389-3.119), and participants carrying two alleles >25 repeats who smoked more than 1 pack-year showed a 1.013-fold higher risk (p = 0.982; 95% confidence interval 0.333-3.084), whereas participants carrying one or two alleles ≤25 repeats who smoked more than 1 pack-year showed a 4.5-fold increased risk for symptomatic IDD (p = 0.005; 95% confidence interval 1.589-12.743). Overall, we observed an underlying additive and multiplicative interaction between the aggrecan gene VNTR polymorphism and smoking in symptomatic IDD.


Occurrence of adverse events in the activity of hospital wards in the opinions of doctors and nursing management staff.
An adverse event is an incident induced while providing health care services or resulting from it, not related to the natural course of a given disease or health condition, which causes or is likely to cause negative consequences for the patient, including their death, a threat to life, the necessity of hospitalisation or its prolongation, permanent or considerable health detriment; or is a foetal disease, congenital defect or the result of foetal damage. The aim of this analysis is to explore the problem of the occurrence of adverse events from the perspective of doctors and ward nurses who manage wards. The research on the occurrence of adverse events among doctors and nurses (the management staff) was conducted with the use of a postal survey. It was ascertained that 86.5% of the medical personnel had taken part in an adverse event, of which 20.2% took part in an occurrence associated with pharmacotherapy, 16.2% - in an event related to diagnostics and diagnosis, or an infection - 15.7%. 14.2% of respondents were involved in an occurrence linked to a medical device malfunction, and 14.1% - in an adverse event related to an operation. The adverse events most often identified in the nursing professional group are occurrences associated with pharmacotherapy, and in the doctors' professional group - occurrences related to diagnostics and diagnosis. The research established that the most frequent reason for not informing patients about the occurrence of an adverse event is fear of their filing a complaint. Medical management staff show high acceptance of an adverse event reporting system as a tool for improving patient safety.


Characteristics and outcomes of elderly patients with Parkinson's disease hospitalized due to COVID‑19‑associated pneumonia.
Patients with Parkinson's disease (PD) and coronavirus disease 2019 (COVID-19)-associated pneumonia present, according to the literature, high mortality rates due to the nature of the disease, advanced age, and underlying diseases. Most available studies, however, refer to the first waves of the pandemic. The aim of the present study was to investigate the clinical characteristics and outcomes of elderly patients (≥65 years old) with PD hospitalized with COVID-19-associated pneumonia during the period of prevalence of various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, as well as to determine possible prognostic factors for poor outcomes. During the period from February 15, 2021, to July 15, 2022, 1,144 elderly patients with COVID-19 pneumonia were hospitalized. Age, sex, Charlson comorbidity index, vaccination status against SARS-CoV-2, and admission laboratory parameters were recorded for all patients. A total of 36 (3.1%) patients with PD were hospitalized due to COVID-19-associated pneumonia (18 males, 50%). The mean age of the patients was 82.72±8.18 years. In total, 8 patients (22.2%) were hospitalized during the period of alpha variant predominance, 3 patients (8.3%) during the period of delta variant predominance, and 25 patients (69.4%) during the omicron variant predominance period. Of note, 16 patients (44.4%) were vaccinated with at least two doses. In addition, 17 (47.2%) patients succumbed to the disease. Between the patients who survived and those who succumbed, a statistically significant difference was only found in the mean value of albumin (37.48±6.02 vs. 31.97±5.34 g/l, P=0.019). In particular, as shown by receiver operating characteristic curve analysis, albumin exhibited a satisfactory predictive ability for mortality (area under the curve, 0.780; P=0.013) with an albumin value ≤37.7 g/l being able to predict mortality with 85.7% sensitivity and 54.8% specificity. Overall, the findings of the present study indicate that mortality among elderly patients with PD hospitalized with COVID-19-associated pneumonia was high in all phases of the pandemic. A low albumin value, not only as an indicator of the immune status, but also of the nutritional status, is a predictor of adverse outcomes.


[Improved information in Medical School may increase recruitment of physician-scientists].
The proportion of physicians undertaking doctoral studies has decreased progressively over the last years both in Sweden and internationally. To counteract this trend, it is important to investigate and improve the recruitment of medical students to research. In the fall of 2012, a questionnaire study investigating interest and involvement in research was conducted among all medical students at Sahlgrenska Academy, Gothenburg University in Sweden. The proportion of students involved in research (16 %) was unchanged from a previous similar study in 2006, and participating in a research project was considered to contribute positively to medical studies. A large number of students (36 %) were interested in conducting research during the semesters, and the main disincentives included lack of time, lack of information, and lack of project and research group. Research stimulating projects such as the 'Amanuensis Program' had a positive impact on research interest in general. For increased and early recruitment of medical students, efforts should be made to offer improved and regular information about conducting research, to publish available research projects and research groups, and to create and expand research programs for motivated medical students. Along with improved conditions and financial resources, we propose that these measures would help to accommodate the growing need for recruitment of medical students and physicians to research.


Current status on the evaluation and management of the highly sensitized kidney transplant recipient.
In light of the recent changes to the kidney allocation system (KAS) and the observed increase in the rate of transplantation of the highly sensitized kidney transplant candidate, the evaluation and care of this population is a timely topic. In its first year, the new KAS has already realized one goal of improving the chances of transplanting the most highly sensitized patients in the waiting list. This has brought to the forefront the need for recipient readiness in this special population, as well as the need for histocompatibility labs and kidney transplant programs to align themselves with each other, and also with the requirements of the United Network for Organ Sharing, and increase proficiency in testing and data interpretation. This manuscript is a review of the literature as well as practice patterns as they relate to the changes in KAS and the observed outcome since the activation of the new KAS, with the ultimate goal of aiding in the development of a more unified approach in the care of this specialized population which will allow for interdisciplinary and cross centre dialogue to optimize long term care and outcomes. Here we will review the changes to the KAS as they affect the highly sensitized kidney transplant recipient, and additional considerations in the evaluation and management of these patients.


Neonatologist-performed point-of-care functional echocardiography in the neonatal intensive care unit.
Functional echocardiography (fECHO) refers to a bedside, limited assessment of the ductus arteriosus, myocardial performance and pulmonary or systemic haemodynamics that is brief in nature and addresses a specific clinical question or management dilemma. This point-of-care ultrasonography is increasingly used internationally and locally among neonatal units to assist with management of neonatal haemodynamic conditions. This article intends to explain the modality, its indications, interpretation and implications for management, and how it impacts long-term outcomes, particularly in chronic lung disease for premature infants born before 32 weeks of gestation. This review will focus on fECHO as a clinical tool to assess the haemodynamics of sick neonates and how it assists in the logical choice for cardiovascular support. Training should be approached as a combined effort between the paediatric cardiology service and neonatology service.


Is It Worth Knowing That You Might Die Tomorrow? Revisiting the Ethics of Prognosis Disclosure.
Ethical discourse on prognosis disclosure is not yet well established. The core of the problem continues to be the dilemma between the right of self-determination and non-maleficence of patients. The prognosis disclosure policy based on Kantian autonomy provides a good solution for the problem. The policy includes demand for strict truth telling and its compatibility with patients' best interest. However, there remains a discrepancy between theory and practice, especially when prognosis is disclosed just prior to their death. Kantian theory of prognosis is supplemented by a moralistic perspective. The moralistic perspective places high importance on temporality and relationships with others, which all human beings inherently possess. From the moralistic viewpoint, decisions about prognosis disclosure at the final stages of life must be individualized in order to be authentically autonomous. The decision to disclose a prognosis or not can only be determined by the relationships fostered over time with patients.


Vocal and semantic cues for the segregation of long concurrent speech stimuli in diotic and dichotic listening-The Long-SWoRD test.
It is not always easy to follow a conversation in a noisy environment. To distinguish between two speakers, a listener must mobilize many perceptual and cognitive processes to maintain attention on a target voice and avoid shifting attention to the background noise. The development of an intelligibility task with long stimuli-the Long-SWoRD test-is introduced. This protocol allows participants to fully benefit from the cognitive resources, such as semantic knowledge, to separate two talkers in a realistic listening environment. Moreover, this task also provides the experimenters with a means to infer fluctuations in auditory selective attention. Two experiments document the performance of normal-hearing listeners in situations where the perceptual separability of the competing voices ranges from easy to hard using a combination of voice and binaural cues. The results show a strong effect of voice differences when the voices are presented diotically. In addition, analyzing the influence of the semantic context on the pattern of responses indicates that the semantic information induces a response bias in situations where the competing voices are distinguishable and indistinguishable from one another.


Peptide length preferences for rat and mouse MHC class I molecules using random peptide libraries.
MHC class I molecules bind short peptides for presentation to CD8+ T cells. The determination of the three-dimensional structure of various MHC class I complexes has revealed that both ends of the peptide binding site are composed of polar residues conserved among all human and murine MHC class I sequences, which act to lock the ends of the peptide into the groove. In the rat, however, differences in these important residues occur, suggesting the possibility that certain rat MHC class I molecules may be able to bind and present longer peptides. Here we have studied the peptide length preferences of two rat MHC class Ia molecules expressed in the TAP2-deficient mouse cell line RMA-S: RT1-A1c, which carries unusual key residues at both ends of the groove, and RT1.Aa which carries the canonical residues. Temperature-dependent peptide stabilization assays were performed using synthetic random peptide libraries of different lengths (7-15 amino acids) and successful stabilization was determined by FACS analysis. Results for two naturally expressed mouse MHC class I molecules revealed different length preferences (H2-Kb, 8-13-mer and H2-Db, 9-15-mer peptides). The rat MHC class Ia molecule, RT1-Aa, revealed a preference for 9-15-mer peptides, whereas RT1-A1c showed a more stringent preference for 9-12-mer peptides, thereby ruling out the hypothesis that unusual residues in rat MHC molecules allow binding of longer peptides.


Micro-CT evaluation of in vivo osteogenesis at implants processed by wire-type electric discharge machining.
Titanium surfaces processed by wire-type electric discharge machining (EDM) are microfabricated surfaces with an irregular morphology, and they exhibited excellent in vitro bone biocompatibility. In this study, the efficiency of in vivo osteogenesis on EDM surfaces was investigated by surgically placing screw-shaped EDM-processed and machined-surface implants into the femurs of four Japanese white rabbits. The volume and process of new bone formation were evaluated by an X-ray micro-CT scanner, coupled with histopathological observations at 1, 2, and 4 weeks post-implantation. Before surgical implantation, the surface topography and contact angle of each implant surface were examined. Bone formation increased over time on both implant surfaces, with both implant types yielding statistically equivalent bone volume at 4 weeks post-implementation. However, at 1 week post-implantation, amount of new bone at EDM-processed implant was markedly greater than that at machined-surface implant. Moreover, new bone appeared to initiate directly from the EDM surfaces, while new bone appeared to generate from pre-existing host bone to the machined surfaces. Thus, EDM seemed to be a promising method for surface modification of titanium implants to support enhanced osteogenesis.


Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced degradation of HMG-CoA reductase.
Cholesterol biosynthesis is tightly regulated in the cell. For example, high sterol concentrations can stimulate degradation of the rate-limiting cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, HMGCR). HMGCR is broken down by the endoplasmic reticulum membrane-associated protein complexes consisting of insulin-induced genes (Insigs) and the E3 ubiquitin ligase gp78. Here we found that HMGCR degradation is partially blunted in Chinese hamster ovary (CHO) cells lacking gp78 (gp78-KO). To identify other ubiquitin ligase(s) that may function together with gp78 in triggering HMGCR degradation, we performed a small-scale short hairpin RNA-based screening targeting endoplasmic reticulum-localized E3s. We found that knockdown of both ring finger protein 145 (Rnf145) and gp78 genes abrogates sterol-induced degradation of HMGCR in CHO cells. We also observed that RNF145 interacts with Insig-1 and -2 proteins and ubiquitinates HMGCR. Moreover, the tetrapeptide sequence YLYF in the sterol-sensing domain and the Cys-537 residue in the RING finger domain were essential for RNF145 binding to Insigs and RNF145 E3 activity, respectively. Of note, amino acid substitutions in the YLYF or of Cys-537 completely abolished RNF145-mediated HMGCR degradation. In summary, our study reveals that RNF145, along with gp78, promotes HMGCR degradation in response to elevated sterol levels and identifies residues essential for RNF145 function.


Commune Health Workers' Methadone Maintenance Treatment (MMT) Knowledge and Perceived Difficulties Providing Decentralized MMT Services in Vietnam.
With the initial establishment of countrywide methadone maintenance therapy (MMT) system, Vietnam is in the process of expanding and decentralizing the MMT program to community-based healthcare settings. The study aimed to measure the MMT-related knowledge and perceived difficulties in treating patient who use drugs (PWUD) among community-based healthcare providers, e.g., commune health workers (CHW), and examine its correlated factors. A total of 300 CHW from 60 communes in two provinces of Vietnam completed a survey using Audio Computer-Assisted Self-Interview (ACASI) method. Twelve true-or-false questions were used to assess the CHW's MMT-related knowledge. The CHW's background characteristics and perceived difficulties treating PWUD were recorded. The mean MMT knowledge score was 8.2 (SD = 1.2; range: 5-11). Misconceptions toward the benefits, procedure, and side effects of MMT were prevalent. The participants perceived varying degrees of difficulties in recruiting, engaging, and communicating with PWUD. With all covariates holding constant, younger age (standardized ẞ = -0.166; p = 0.0078) was associated with less MMT-related knowledge. Number of PWUD seen in a month and MMT-related knowledge was associated with less perceived difficulties treating PWUD. Conclusions/importance: The finding shed lights on the CHW's knowledge gap, which need to be addressed to facilitate the decentralization of MMT services in Vietnam. In preparation for a decentralized MMT service delivery model, specially designed training is warranted to equip CHW with knowledge and confidence to provide MMT-related services to PWUD.


Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis and Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress Signaling Pathway.
Methamphetamine (METH) is an illegal and widely abused psychoactive stimulant. METH exposure causes detrimental effects on multiple organ systems, primarily the nervous system, especially dopaminergic pathways, in both laboratory animals and humans. In this study, we hypothesized that Nuclear protein 1 (Nupr1/com1/p8) is involved in METH-induced neuronal apoptosis and autophagy through endoplasmic reticulum (ER) stress signaling pathway. To test this hypothesis, we measured the expression levels of Nupr1, ER stress protein markers CHOP and Trib3, apoptosis-related protein markers cleaved-caspase3 and PARP, as well as autophagy-related protein markers LC3 and Beclin-1 in brain tissues of adult male Sprague-Dawley (SD) rats, rat primary cultured neurons and the rat adrenal pheochromocytoma cells (PC12 cells) after METH exposure. We also determined the effects of METH exposure on the expression of these proteins after silencing Nupr1, CHOP, or Trib3 expression with synthetic small hairpin RNA (shRNA) or siRNA in vitro, and after silencing Nupr1 in the striatum of rats by injecting lentivirus containing shRNA sequence targeting Nupr1 gene to rat striatum. The results showed that METH exposure increased Nupr1 expression that was accompanied with increased expression of ER stress protein markers CHOP and Trib3, and also led to apoptosis and autophagy in rat primary neurons and in PC12 cells after 24 h exposure (3.0 mM), and in the prefrontal cortex and striatum of rats after repeated intraperitoneal injections (15 mg/kg × 8 injections at 12 h intervals). Silencing of Nupr1 expression partly reduced METH-induced apoptosis and autophagy in vitro and in vivo. These results suggest that Nupr1 plays an essential role in METH-caused neuronal apoptosis and autophagy at relatively higher doses and may be a potential therapeutic target in high-dose METH-induced neurotoxicity.


Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid.
The vast industrial use of nickel has led to environmental pollution by the metal and its by-products during production, recycling, and disposal. Nickel is a known hematotoxic, immunotoxic, hepatotoxic, pulmotoxic, and nephrotoxic agent. Allergic skin reactions are common in individuals who are sensitive to nickel. This article presents a selective review on nickel and its effect on certain metabolically active peripheral tissues of human and animals. The subtopics include nickel sources and uses, exposure pathways, transport, excretion, general health effects, and specific acute and chronic nickel toxicities in peripheral tissues like liver, lungs, and kidneys. The review particularly addresses the nickel-induced generation of reactive oxygen species and increased lipid peroxidation in various metabolically active tissues in humans and animals, and the possible role of vitamin c as a protective antioxidant.


Study of Relationship between Bone Mineral Density in Ipsilateral Proximal Femur and Severity of Osteoarthritis of Knee.
Osteoarthritis (OA) of the knee is the most common rheumatic disease that is characterized by degradation of articular cartilage, subchondral bone alteration, meniscal degeneration, synovial inflammatory response, and overgrowth of bone and cartilage. In severe OA, the reduced mobility caused by pain can increase bone loss and reduction of bone mineral density leading to osteoporosis. To examine the possible relationship between severity of osteoarthritis (OA) and bone mineral density (BMD) by evaluating the bone mineral density in ipsilateral proximal femur and radiographic grading of knee OA in the Indian population. In this cross-sectional observational study, 100 subjects diagnosed with OA knee using ACR criteria were enrolled. Severity of OA knee was assessed using Kellgren-Lawrence scale (1 to 4) on weight-bearing radiographs. The BMD, T-score, and Z-score of the ipsilateral proximal femur was measured by dual-energy X-ray absorptiometry. Pearson's correlation coefficient was used to test the association of severity of OA knee with BMD. Among 100 subjects, there were 51 females and 49 males with mean age 59.94 ± 6.67. Maximum patients were with K-L grade 2 (42%) followed by grade 3 (30%) and grade 4 (22%). There was statistically significant (p < 0.0001) association between BMD and severity of OA knee. BMD decreased as the K-L grade of OA knee increased from 1 to 4. Similar statistically significant association was observed in T-score and Z-score. The study concluded that BMD of ipsilateral proximal femur decreases with severity of OA knee. These data support the fact that the two conditions may be related to each other and primary care physicians must look for these two conditions in coexistence. Primary prevention of either of the two conditions should be advised, if the other condition coexists in the same patient.


Gravure-Offset Printed Metallization of Multi-Crystalline Silicon Solar Cells with Low Metal-Line Width for Mass Production.
The gravure offset method has been developed toward an industrially viable printing technique for electronic circuitry. In this paper, a roller type gravure offset manufacturing process was developed to fabricate fine line for using front electrode for solar cells. In order to obtain the optimum metallization printing lines, thickness of 20 μm which is narrow line is required. The main targets are the reduction of metallized area to reduce the shading loss, and a high conductivity to transport the current as loss free as possible out of the cell. However, it is well known that there is a poor contact resistance between the front Ag electrode and the n(+) emitter. Nickel plating was conducted to prevent the increase of contact resistance and the increase of fill factor (FF). The performance of n-Si/Ag (seed layer)/Ni solar cells were observed in 609 mV of open circuit voltage, 35.54 mA/cm2 of short circuit current density, 75.75% of fill factor, and 16.04% of conversion efficiency.


Incidence and predictors of hypophosphataemia after ferric carboxymaltose use-A 3-year experience from a single institution in Singapore.
Ferric carboxymaltose (FCM) administration helps reduce transfusion requirements in the perioperative situation, which improves patient outcomes and reduces healthcare costs. However, there is increasing evidence of hypophosphataemia after FCM use. We aim to determine the incidence of hypophosphataemia after FCM administration and elucidate potential biochemical factors associated with the development of subsequent hypophosphataemia. A retrospective review of anonymised data of all FCM administrations in a single institution was conducted from August 2018 to August 2021. Each unique FCM dose administered was examined to assess its effect on Hb and serum phosphate levels within the subsequent 28 days from each FCM administration. Phosphate levels were repeatedly measured within the 28-day interval and the lowest phosphate level within that period was determined. Patients' serum phosphate levels within 28 days of FCM administration were compared against normal serum phosphate levels within 2 weeks before FCM administration. The odds ratios of various pre-FCM serum markers were calculated to elucidate potential biochemical predictors of post-FCM hypophosphataemia. In 3 years, a total of 1296 doses of FCM were administered to 1069 patients. The mean improvement in Hb was 2.45 g/dL (SD = 1.94) within 28 days of FCM administration, with the mean time taken to peak Hb levels being 6.3 days (SD = 8.63), which is earlier than expected, but was observed in this study and hence reported. The incidence of hypophosphataemia <0.8 mmol/L was 22.7% (n = 186), and <0.4 mmol/L was 1.6% (n = 9). This figure is lower than the numbers reported in previously published meta-analyses given that routine checks of serum phosphate levels were not conducted initially and hence could possibly be higher. The odds of developing hypophosphataemia (<0.8 mmol/L) were 27.7 (CI: 17.3-44.2, p < 0.0001) if baseline serum phosphate was less than 1 mmol/L. The odds of developing hypophosphataemia (<0.8 mmol/L) were 1.3 (CI: 1.08-1.59, p < 0.01) if the change in Hb levels observed after FCM administration were more than 4 g/dL. Hypophosphataemia after FCM administration is significant and FCM should be used by clinicians with caution.