Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076.
Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B-containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC 13636, and Salmonella enteritidis ATCC 13076 was evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The synthetic bovine lactoferricin exhibited antibacterial activity against E. coli ATCC 11775 and S. enteritidis ATCC 13076. The dimeric peptide (RRWQWR)₂K-Ahx exhibited the highest antibacterial activity against the tested bacterial strain. The monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif exhibited high and specific activity against E. coli ATCC 11775. The results suggest that short peptides derived from lactoferricin B could be considered as potential candidates for the development of antibacterial agents against infections caused by E. coli.


Effect of environmental temperature on semen quality and seminal plasma metabolites of Mediterranean buffalo bulls.
High-quality semen with high viability is critical to improving the in-vitro fertilization efficiency. This study aimed to understand the effect of ambient temperature and humidity on semen quality and seminal plasma biochemical parameters of Mediterranean buffalo in March and July. The metabolites of seminal plasma in two seasons were detected using the UPLC-MS/MS method. The results showed that temperature and humidity index (THI) in March were 66.86 ± 2.98, and 82.94 ± 3.52 in July. Compared with in March, breath frequency, rectal temperature, and heat shock protein 70 expressions of seminal plasma were significantly increased in July (p < 0.05), motility of sperm was dramatically reduced, and sperm deformity rate was significantly increased (p < 0.05). Fructose, acid phosphatase and α-glucosidase in seminal plasma were significantly increased (p < 0.05) in July, while testosterone level was significantly reduced (p < 0.05). Six different metabolites were found in the two groups, which involved in three metabolic pathways, the tricarboxylic acid cycle, glycerophospholipid, glyoxylic acid and dicarboxylic acid. The above results indicate that the increased ambient temperature has obvious side effects on the semen quality of Mediterranean buffalo, and the compromised quality is associated with the change of metabolites related to male hormone secretion, energy metabolism and fatty acid oxidation.


Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α.
PPARα is well known as a master regulator of lipid metabolism. PPARα activation enhances fatty acid oxidation and decreases the levels of circulating and cellular lipids in obese diabetic patients. Although PPARα target genes are widely known, little is known about the alteration of plasma and liver metabolites during PPARα activation. Here, we report that metabolome analysis-implicated upregulation of many plasma lysoGP species during bezafibrate (PPARα agonist) treatment. In particular, 1-palmitoyl lysophosphatidylcholine [LPC(16:0)] is increased by bezafibrate treatment in both plasma and liver. In mouse primary hepatocytes, the secretion of LPC(16:0) increased on PPARα activation, and this effect was attenuated by PPARα antagonist treatment. We demonstrated that Pla2g7 gene expression levels in the murine hepatocytes were increased by PPARα activation, and the secretion of LPC(16:0) was suppressed by Pla2g7 siRNA treatment. Interestingly, LPC(16:0) activates PPARα and induces the expression of PPARα target genes in hepatocytes. Furthermore, we showed that LPC(16:0) has the ability to recover glucose uptake in adipocytes induced insulin resistance. These results reveal that LPC(16:0) is induced by PPARα activation in hepatocytes; LPC(16:0) contributes to the upregulation of PPARα target genes in hepatocytes and the recovery of glucose uptake in insulin-resistant adipocytes.


European atmospheric pollution imported by cooler air masses to the Eastern Mediterranean during the summer.
In this study we combine Pb isotopes, Pb, Ni, Cu, Zn, and several major metal concentrations, identification of the aerosol particles, and synoptic and back trajectory analyses to obtain direct evidence for the extent and nature of mixing between Middle Eastern and European sources emissions of metals and aerosols. During the summer months aerosols collected in Israel are highly polluted by metals (EF(Ni) = 120, EF(Cu) = 320, EF(Zn) = 30, EF(Pb) = 540; average values). The fraction of European Pb of mostly industrial sources is 61 +/- 21% in Jerusalem, and the fraction of European Cu, Zn, Ni, and aerosols should be on the same order. Whenever a steep pressure gradient is built between the barometric trough originating from the Persian Gulf and the subtropical ridge along the African coast, stronger westerly winds and cooler temperatures (deep Persian Trough) prevail overthe Middle East, and higher amounts of European pollution are observed in the atmosphere (74 +/- 13%). On the other hand, when the Persian Trough is in its shallow mode, the proportion of European pollution is lower (45 +/- 18%, based on Pb isotopes). This study demonstrates that atmospheric pollution over the East Mediterranean region during the summer is influenced not only by local atmospheric dispersion conditions but also by the ability of the atmosphere to inherit a significant proportion of pollutants from European sources.


Development, Management and Utilization of a Kiwifruit (Actinidia spp.) In Vitro Collection: A New Zealand Perspective.
The New Zealand Institute for Plant and Food Research Limited (PFR) supports a large kiwifruit breeding program that includes more than twenty Actinidia species. Almost all the kiwifruit accessions are held as field collections across a range of locations, though not all plants are at multiple locations. An in vitro collection of kiwifruit in New Zealand was established upon the arrival of Pseudomonas syringae pv. Actinadiae-biovar 3 in 2010. The value of an in vitro collection has been emphasized by restrictions on importation of new plants into New Zealand and increasing awareness of the array of biotic and abiotic threats to field collections. The PFR in vitro collection currently holds about 450 genotypes from various species, mostly A. chinensis var. chinensis and A. chinensis var. deliciosa. These collections and the in vitro facilities are used for germplasm conservation, identification of disease-free plants, reference collections and making plants available to users. Management of such a diverse collection requires appropriate protocols, excellent documentation, training, sample tracking and databasing and true-to-type testing, as well as specialized facilities and resources. This review also discusses the New Zealand biosecurity and compliance regime governing kiwifruit plant movement, and how protocols employed by the facility aid the movement of pathogen-free plants within and from New Zealand.


Unraveling the functional consequences of a novel germline missense mutation (R38C) in the yeast model of succinate dehydrogenase subunit B: insights into neurodegenerative disorders.
This study explores the implications of a novel germline missense mutation (R38C) in the succinate dehydrogenase (SDH) subunit B, which has been linked to neurodegenerative diseases. The mutation was identified from the SDH mutation database and corresponds to the SDH2R32C allele, mirroring the human SDHBR38C mutation. By subjecting the mutant yeast model to hydrogen peroxide (H2O2) stress, simulating oxidative stress, we observed heightened sensitivity to oxidative conditions. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed significant regulation (p < 0.05) of genes associated with antioxidant systems and energy metabolism. Through gas chromatography-mass spectrometry (GC-MS) analysis, we examined yeast cell metabolites under oxidative stress, uncovering insights into the potential protective role of o-vanillin. This study elucidates the biological mechanisms underlying cellular oxidative stress responses, offering valuable insights into its repercussions. These findings shed light on innovative avenues for addressing neurodegenerative diseases, potentially revolutionizing therapeutic strategies.


Electrically insulated sensing of respiratory rate and heartbeat using optical fibers.
Respiratory and heart rates are among the most important physiological parameters used to monitor patients' health. It is important to design devices that can measure these parameters without risking or altering the subject's health. In this context, a novel sensing method to monitor simultaneously the heartbeat and respiratory rate signals of patients within an electrically safety environment was developed and tested. An optical fiber-based sensor was used in order to detect two optical phenomena. Photo-plethysmography and the relation between bending radius and attenuation of optical fiber were coupled through a single beam light traveling along this fiber.


[Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia].
Hyperhomocysteinemia is associated to thrombosis and atherosclerosis. Vitamin B12 is among its main causes and may be due to a pernicious anemia. This study aimed to know the prevalence of this disease in patients who have venous thromboembolism and hyperhomocysteinemia. A total of 80 consecutive patients (55 men and 25 women; age: mean [standard deviation] 63 [15] years) with pulmonary embolism and/or venous thrombosis and elevated values of homocysteine (> 12 micromol/l) were studied. Pernicious anemia was diagnosed (positive Schilling test, presence of anti-intrinsic factor antibodies and/or anti-parietal cells and fundal atrophic gastritis) in 5 patients (6.25% with range of age: 42-73 years. Only one of them had macrocytic anemia and there were no alterations in any of them in the thrombophilia study. The patients were treated with vitamin B12, administering it orally (1 mg/day) in 4 of them. The homocysteine and vitamin B12 values were normalized in every case at 6 months. Although the prevalence of pernicious anemia is not elevated in patients with venous thromboembolism and hyperhomocysteinemia, its existence must be ruled out to avoid other thrombotic and neurological complications.


Immune check point inhibitors in advanced cutaneous squamous cell carcinomas: "Repeat and replicate".
Recent evidence confirmed the significant clinical benefit from using immune check point inhibitors, namely PD-1 inhibitors, in patients with advanced cutaneous squamous cell carcinomas. The activity of these different agents seems to be strikingly equivalent. This phase 2 trial confirms a similar clinical benefit to single agent nivolumab in treating this disease. The replication of these findings raises the question of whether substitution of these immunotherapeutic agents can be justified based on smaller confirmatory trials.


Prognostic significance of c-erbB-2 gene expression in the poorly differentiated type of adenocarcinoma of the stomach.
Prognostic significance of c-erbB-2 gene abnormalities is unclear in the poorly differentiated type of gastric carcinoma, because the abnormalities of this gene have been reported to be restricted to the differentiated type of gastric carcinoma. In this study, correlation of c-erbB-2 gene amplification/overexpression of mRNA and protein were studied in the poorly differentiated type of gastric carcinoma. c-erbB-2 gene amplification determined by the slot-blot hybridization was observed in 11 (13%) of 82 gastric cancer, and 8 of 11 tumors were poorly differentiated. In addition, c-erbB-2 mRNA expression was studied by the reverse transcriptase-polymerase chain reaction. Four (17%) of 24 tumors showed overexpression of c-erbB-2 mRNA, and all these four exhibited morphologically a poorly differentiated type. Among 157 poorly differentiated gastric cancers, 20 (13%) tumors showed immunohistochemically c-erbB-2 protein expression. These tumors had significantly higher incidences of larger tumor, serosal invasion-positive tumors, node-positive tumor, or peritoneal dissemination-positive tumor than those without c-erbB-2 expression. Furthermore, patients with c-erbB-2 protein overexpression ran poorer prognoses than those without c-erbB-2 expression. From these results, we conclude that expression c-erbB-2 tissue status may be a good prognostic indicator in poorly differentiated gastric carcinoma.


Maternal responsiveness and maternal selectivity in domestic sheep and goats: the two facets of maternal attachment.
Sheep and goats rapidly establish an exclusive relationship with their neonate following contact with it during a sensitive period of maternal responsiveness induced by the physiological events occurring at parturition. The data concerning the sensory, physiological, and neurobiological factors involved in the activation of both maternal responsiveness and the establishment of selective nursing indicates that these processes are activated simultaneously by the combined action of two main factors, the prepartum rise in circulating estrogen and the vaginocervical stimulation (VCS) caused by fetus expulsion. On the one hand, these two factors act on a neural network including the main olfactory system (MOB), the medial preoptic area (MPOA), and the paraventricular nucleus of the hypothalamus (PVN) to induce maternal responsiveness towards any neonate. The intracerebral release of oxytocin (OT) from the PVN, and the triggering of olfactory attraction for amniotic fluid (AF) are key elements in this process. On the other hand, VCS at birth also sets the MOB ready to memorize the individual odor of the neonate, through the release of peptides and neurotransmitters (noradrenaline and acetylcholine). In addition to the MOB, the network involved in recognition mainly includes the medial and cortical amygdala. Across consolidation processes, reorganization occurs in the network engaged in lamb recognition. Whether this memorization may be potentiated by other sensory cues is not known. The identification of the chemosensory compounds involved in the attraction for AF and in the recognition of the neonate is important for understanding the mechanisms of maternal attachment.


Two-in-one aortic valve sizing and valvuloplasty conductance balloon catheter.
Inaccurate aortic valve sizing and selection is linked to paravalvular leakage in transcatheter aortic valve replacement (TAVR). Here, a novel sizing valvuloplasty conductance balloon (SVCB) catheter is shown to be accurate, reproducible, unbiased, and provides real-time tool for aortic valve sizing that fits within the standard valvuloplasty procedure. The SVCB catheter is a valvuloplasty device that uses real-time electrical conductance measurements based on Ohm's Law to size the balloon opposed against the aortic valve at any given inflation pressure. Accuracy and repeatability of the SVCB catheter was performed on the bench in phantoms of known dimension and ex vivo in three domestic swine aortic annuli with comparison to computed tomography (CT) and dilator measurements. Procedural workflow and safety was demonstrated in vivo in three additional domestic swine. SVCB catheter measurements had negligible bias or error for bench accuracy considered as the gold standard (Bias: -0.11 ± 0.26 mm; Error: 1.2%), but greater disagreement in ex vivo versus dilators (Bias: -0.3 ± 1.1 mm; Error: 4.5%), and ex vivo versus CT (Bias: -1.0 ± 1.6 mm; Error: 8.7%). The dilator versus CT accuracy showed similar agreement (Bias: -0.9 ± 1.5 mm; Error: 7.3%). Repeatability was excellent on the bench (Bias: 0.02 ± 0.12 mm; Error: 0.5%) and ex vivo (Bias: -0.4 ± 0.9 mm; Error: 4.6%). In animal studies, the device fit well within the procedural workflow with no adverse events or complications. Due to the clinical relevance of this accurate, repeatable, unbiased, and real-time sizing measurement, the SVCB catheter may provide a useful tool prior to TAVR. These findings merit a future human study.


[Post-thymectomy extrathymic tumors].
The Authors report the case of a 78 year old woman affected with two synchronous primary cancers (epidermoid bronchial and rectal adenocarcinoma); 16 years previously, after the discovery of a thymoma, she underwent thymectomy. Thus, the discussion issue is if post-thymectomy extra-thymic malignancies are to be considered just a simple coincidence or a true syndrome.


Tailored pre-procedural management and four-clip trans-catheter edge-to-edge repair procedure to efficiently treat torrential tricuspid regurgitation: a case report.
The use of trans-catheter treatment for tricuspid regurgitation (TR) is currently increasing, especially trans-catheter edge-to-edge repair (TEER). However, patients with very large coaptation gaps are usually considered not eligible for this treatment. We present the case of an 87-year-old man with symptomatic [New York Heart Association (NYHA) functional Class IV, right-sided heart failure signs] isolated torrential TR due to chronic atrial fibrillation who was initially considered not eligible for a tricuspid valve (TV) TEER because of a very large coaptation gap. A leadless pacemaker was implanted, and the patient received high doses of intravenous diuretics at home during 2 months. After heart team discussion, he was then considered suitable for a TEER procedure. A 'zipping' technique was performed, with the implantation of four TriClip devices, based on the anatomy of the TV and guided by fluoroscopy and bi- and tri-dimensional trans-oesophageal echocardiography, allowing an excellent procedural result (mild TR and mean TV gradient = 1 mmHg). At 6 months, TR was still mild, the patient reported a remarkable improvement (NYHA I, no heart failure signs), and 6-min walk test increased from 260 to 375 m. This case underscores the need for heart valve centres with dedicated and experienced teams and networks of care to adequately manage patients with severe TR from pre-procedural choice of cardiac pacing type and optimization of diuretic therapy to customized interventions with appropriate number and location of clips according to the anatomy of the valve and the mechanism of TR, guided by high-quality bi- and tri-dimensional echocardiography.


Prevalence of gram negative anaerobic bacilli in routine clinical specimens.
A total of 206 gram negative anaerobic bacilli were isolated from 2591 routine clinical specimens. Majority of them (78.2%) were part of a mixed flora. A high incidence of gram negative anaerobic bacilli was found in post-operative wound infections and diabetic foot infections (30.1%), followed by necrotizing fasciitis and crush injuries (18%), pus of empyema and lung abscesses (14.5%) and aspirates from other deep abscesses (10.7%). Bacteroides fragilis was the most frequently recognized species (42.2%), followed by Fusobacterium sp. (17.4%), Prevotella sp. (15.1%) and Porphyromonas sp. (11.2%). Neomycin blood agar plate yielded the maximum number (72.8%) of strains in pure culture. Gram negative anaerobic bacilli in infective processes are significantly on the rise and so suspected cultures should be processed for both aerobic and anaerobic organisms.


Tea Polyphenols Enhanced the Antioxidant Capacity and Induced Hsps to Relieve Heat Stress Injury.
Keap1-Nrf2-ARE and heat shock proteins (Hsps) are important endogenous protection mechanisms initiated by heat stress to play a double protective role for cell adaptation and survival. H9C2 cells and 80 300-day-old specific pathogen-free chickens were randomly divided into the control and tea polyphenol groups and used to establish a heat stress model in vitro and in vivo. This task was conducted to explore the protection and mechanism of tea polyphenols in relieving thermal injury. A supplement with 10 μg/mL tea polyphenols could effectively relieve the heat damage of H9C2 cells at 42°C. Accordingly, weaker granular degeneration, vacuolar degeneration, and nucleus deep staining were shown. A strong antioxidant capacity was manifested in the upregulation of the total antioxidant capacity (T-AOC) (at 5 h, P < 0.05), Hemeoxygenase-1 mRNA (at 2 h, P < 0.01), superoxide dismutase (SOD) (at 2, 3, and 5 h, P < 0.05), and Nrf2 (at 0 and 5 h, P < 0.01). A high expression of Hsps was reflected in CRYAB at 3 h; Hsp27 at 0, 2, and 3 h (P < 0.01); and Hsp70 at 3 and 5 h (P < 0.01). The supplement with 0.2 g/L tea polyphenols in the drinking water also had a good effect in alleviating the heat stress damage of the myocardial cells of hens at 38°C. Accordingly, light pathological lesions and downregulation of the myocardial injury-related indicators (LDH, CK, CK-MB, and TNF-α) were shown. The mechanism was related to the upregulation of T-AOC (at 0 h, P < 0.05), GSH-PX (at 0.5 d, P < 0.01), SOD (at 0.5 d), and Nrf2 (at 0 d with P < 0.01 and 2 d with P < 0.05) and the induced expression of CRYAB (at 0.5 and 2 d), Hsp27 (at 0, 0.5, and 5 d), and Hsp70 (at 0 and 0.5 d). In conclusion, the tea polyphenols enhanced the antioxidant capacity and induced Hsps to relieve heat stress injury.


[Molecular features of breast cancer predictive of lymph node metastases].
The aim of our study was to analyze morphologic and molecular markers of breast cancer relating them to the presence of metastases in axillary lymph nodes. We selected 123 cases of invasive mammary carcinomas stratified into three subgroups: with macrometastases, with micrometastases, and lymph node negative. Presence of metastases was evaluated relating them with morphologic factors (size of primary tumor, type and grade, presence of lymphatic and blood vessel invasion in hematoxylin and eosin-stained slides) and molecular factors of primary tumor (estrogen and progesterone receptors, E-cadherin, Ki67, p53, Her2 expression, and the presence of lymphatic and blood vessel invasion in immunostained sections for D2-40 and CD31). Axillary lymph node metastases were positively related to the presence of lymphatic vessel invasion in hematoxylin and eosin (H&E)-stained slides, when analyzed with or without metastases (p=0.04) and when analyzed in the three subgroups (p=0.002). Lymph node metastases were also positively related to presence of blood vessel invasion identified by immunohistochemistry (IHC) for CD31 (p=0.02). However other morphologic and molecular factors were not related to the presence of axillary node metastases. Lymphatic and blood vessel invasion identified in H&E and IHC-stained slides are positively related to the rmetastatic status of axillary lymph nodes and are predictive of axillary lymph node metastases in breast cancer.


[Sexuality of the elderly].
After reminding briefly physiological changes in the elderly's sexual life, a few normal and pathological attitudes are considered, as well as the reactions of the environment. At the same time, it is impossible to describe this varied sexuality in a single configuration of characteristics.


Lipid metabolism in chronic kidney disease: the role of statins in cardiovascular risk.
In the general population, the relation between lipids and cardiovascular disease is clearcut, whereas it is highly controversial in chronic kidney disease (CKD) patients. This is primarily due to diverging results of retrospective observational trials. This study design often encounters confounding, especially in renal disease patients. Even if analyses are corrected for multiple influences, there might be unknown confounders changing the results. Prospective randomized trials assure that groups are comparable except for the intervention used. Confounding is eliminated by randomization. Nevertheless, the lipid discussion was restarted when two randomized, placebo-controlled, interventional trials on lipid-lowering therapy in renal patients have been published (Assessment of Lescol in Renal Transplantation and 4D Study [Atorvastatin in patients with type 2 diabetes on hemodialysis]). Surprisingly, both showed no significant reduction of the primary endpoint by statin therapy. In addition to other factors, this might be due to an altered pathogenesis of atherosclerosis in renal patients where multiple nontraditional cardiovascular risk factors are to be mentioned and different characteristics of cardiovascular disease with a high proportion of sudden cardiac death are present. This review will focus on dyslipidemia in renal failure and its treatment. The data published so far is summarized and grouped according to the different stages of CKD.


Management of skin conditions in the older population 2.
This is the second of two papers covering assessment and management of elderly skin. Part 1 of this clinical review focused on the importance of a comprehensive assessment of the skin and a detailed clinical history of the patient (Bianchi and Cameron, 2008). This second paper considers some common dermatological conditions seen in the older adult and explores suitable management strategies.


Translation, Cross-Cultural Adaptation, and Measurement Properties of the Brazilian-Portuguese Version of the Fear of Falling Avoidance Behavior Questionnaire in Older Adults.
The aim of this study was to translate and culturally adapt the Fear of Falling Avoidance Behavior Questionnaire (FFABQ) into Brazilian-Portuguese (FFABQ-B), and to examine its reliability and validity in Brazilian older adults. The FFABQ-B was translated and tested in 10 Brazilian older adults. We assessed 52 community-dwellers, 68.7 (±6.2) years, using the FFABQ-B, BERG Balance Scale, Activities-specific Balance Confidence Scale, Falls Efficacy Scale, 6-Minute Walk Test, Timed Up and Go test, and activity monitor. Internal consistency, test-retest reliability, construct validity, and floor and ceiling effects were analyzed. The FFABQ-B had adequate internal consistency (Cronbach's α = .90) and test-retest reliability (intraclass correlation coefficient = .81; 95% confidence interval [.68, .90]). The FFABQ-B was associated with 6-Minute Walk Test, Timed Up and Go, BERG Balance Scale, physical activity time (p < .05), Activities-specific Balance Confidence scale, and Falls Efficacy Scale (p < .001). The FFABQ-B is both reliable and valid to assess avoidance behavior in activities and participation due to fear of falling in Brazilian community-dwelling older adults.


Pyrazolopyrimidine metabolism in Leishmania and trypanosomes: significant differences between host and parasite.
The pathogenic hemoflagellates of the genera Leishmania and Trypanosoma are major causes of human disease in the tropical and subtropical areas of the world. In general, the agents used to treat diseases caused by these organisms are toxic and not suitable for administration to the millions of people infected. Investigations over the past several years have shown that there are several major differences between man and these protozoans with respect to purine metabolism. The differences appear to offer promise for the development of effective chemotherapeutic compounds. These organisms do not synthesize purines de novo, as does man. They are able to concentrate pyrazolopyrimidines with the cell and metabolize them as purines through the salvage pathways, ultimately incorporating them into nucleic acids. This does not occur in mammals. The pyrazolopyrimidine base allopurinol, which has served as a prototype, is activated by a phosphoribosyltransferase to the ribonucleotide. The ribonucleotide is aminated to the 4-amino-pyrazolopyrimidine ribonucleotide and subsequently phosphorylated to the triphosphate form and incorporated into RNA. The pyrazolopyrimidine ribonucleosides formycin B and allopurinol ribonucleoside are activated through a nucleoside phosphotransferase. The resulting ribonucleotide is aminated and incorporated into RNA as described above. These metabolic peculiarities occur not only in the forms of these parasites which are found in the insect vectors but also in the intracellular forms which are pathogenic in man. The differences in the enzymology and metabolism of purines which exist in the genera Leishmania and Trypanosoma offer excellent opportunities for chemotherapeutic exploitation.


Spinal astrocytic MeCP2 regulates Kir4.1 for the maintenance of chronic hyperalgesia in neuropathic pain.
Astrocyte activation in the spinal dorsal horn may play an important role in the development of chronic neuropathic pain, but the mechanisms involved in astrocyte activation and their modulatory effects remain unknown. The inward rectifying potassium channel protein 4.1 (Kir4.1) is the most important background K+ channel in astrocytes. However, how Kir4.1 is regulated and contributes to behavioral hyperalgesia in chronic pain is unknown. In this study, single-cell RNA sequencing analysis indicated that the expression levels of both Kir4.1 and Methyl-CpG-binding protein 2 (MeCP2) were decreased in spinal astrocytes after chronic constriction injury (CCI) in a mouse model. Conditional knockout of the Kir4.1 channel in spinal astrocytes led to hyperalgesia, and overexpression of the Kir4.1 channel in spinal cord relieved CCI-induced hyperalgesia. Expression of spinal Kir4.1 after CCI was regulated by MeCP2. Electrophysiological recording in spinal slices showed that knockdown of Kir4.1 significantly up-regulated the excitability of astrocytes and then functionally changed the firing patterns of neurons in dorsal spinal cord. Therefore, targeting spinal Kir4.1 may be a therapeutic approach for hyperalgesia in chronic neuropathic pain.


Increased excretion of urinary glycosaminoglycans in a case of Rothmund Thomson syndrome.
The exercretion of urinary total glycosaminoglycans (GAG) in a case of Rothmund Thomson syndrome associated with osteosarcoma was increased about 2--3 times that of normal control. Since the excretion of urinary total GAG in two cases of osteosarcoma was within normal range, the increased excretion of total GAG might be on account of the metabolic disorder of GAG in Rothmund Thomson syndrome. The prominent fractions obtained by Dowex 1 column chromatography from this syndrome were 0.75 M Fr and 1.0 M Fr, in which the major GAG were indicated to be partially degraded forms of heparan sulfate and chondroitin sulfate, respectively.


Misunderstandings and misinterpretations: Antimicrobial use and resistance in salmon aquaculture.
The exponential growth of aquaculture over the past 30 years has been accompanied by a parallel increase in the use of antimicrobials. This widespread use has had negative effects on animal, human and environmental health and affected the biodiversity of the environments where aquaculture takes place. Results showing these harmful effects have been resisted and made light of by the aquaculture industry and their scientific supporters through introduction of misunderstandings and misinterpretations of concepts developed in the evolution, genetics, and molecular epidemiology of antimicrobial resistance. We focus on a few of the most obvious scientific shortcomings and biases of two recent attempts to minimise the negative impacts of excessive antimicrobial use in Chilean salmon aquaculture on human and piscine health and on the environment. Such open debate is critical to timely implementation of effective regulation of antimicrobial usage in salmon aquaculture in Chile, if the negative local and worldwide impacts of this usage are to be avoided.


Intrinsic Brain Activity Responsible for Sex Differences in Shyness and Social Anxiety.
Male and female show significant differences in important behavioral features such as shyness, yet the neural substrates of these differences remain poorly understood. Previous neuroimaging studies have demonstrated that both shyness and social anxiety in healthy subjects are associated with increased activation in the fronto-limbic and cognitive control areas. However, it remains unknown whether these brain abnormalities would be shared by different genders. Therefore, in the current study, we used resting-state fMRI (r-fMRI) to investigate sex differences in intrinsic cerebral activity that may contribute to shyness and social anxiety. Sixty subjects (28 males, 32 females) participated in r-fMRI scans, and the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) were used to measure the spontaneous regional cerebral activity in all subjects. We first compared the differences between male and female both in the ALFF and fALFF and then we also examined the whole brain correlation between the ALFF/fALFF and the severity of shyness as well as social anxiety by genders. Referring to shyness measure, we found a significant positive correlation between shyness scores (CBSS) and ALFF/fALFF value in the frontoparietal control network and a negative correlation in the cingulo-insular network in female; while in male, there is no such correlation. For the social anxiety level, we found positive correlations between Leibowitz Social Anxiety Scale (LSAS) scores and spontaneous activity in the frontal-limbic network in male and negative correlation between the frontal-parietal network; however, such correlation was not prominent in female. This pattern suggests that shy female individuals engaged a proactive control process, driven by a positive association with activity in frontoparietal network and negative association in cingulo-insular network, whereas social anxiety males relied more on a reactive control process, driven by a positive correlation of frontal-limbic network and negative correlation of frontoparietal network. Our results reveal that shyness or social anxiety is associated with disrupted spontaneous brain activity patterns and that these patterns are influenced by sex.


Molecular identification of host feeding patterns of snow-melt mosquitoes (Diptera: Culicidae): potential implications for the transmission ecology of Jamestown Canyon virus.
We collected blood-fed, snow-melt mosquitoes (Culicidae: Culiseta and Aedes) to describe the feeding patterns of potential mosquito vectors of Jamestown Canyon virus (JCV, Bunyaviridae: Orthobunyavirus). JCV is an arthropod-borne, zoonotic virus with deer as the primary amplifying host in western alpine ecosystems. We collected mosquitoes from natural resting areas, fiber pots, and carbon-dioxide baited miniature light traps in the Colorado Rocky Mountains in 2007. We conducted two polymerase chain reactions to amplify and sequence vertebrate DNA extracted from blood-fed mosquitoes, which yielded comparable, but not identical, results. Mammal-specific primers found mule deer (Odocoileus hemionus) and elk (Cervus elaphus canadensis) as the source of all bloodmeals. To determine if unamplified bloodmeals were from nonmammalian sources, we screened all samples with conserved vertebrate primers, which confirmed the initial polymerase chain reaction results, but also found porcupine (Erethizon dorsatum) and human (Homo sapiens) as additional bloodmeal sources. We consistently found that mule deer were the primary hosts for mosquitoes in this system. These results suggest that snow-melt mosquitoes, in particular A. cataphylla, may be important vectors in western JCV alpine systems and may also act as a bridge vector for JCV from cervid virus reservoirs to humans.


[Evaluation of brain dysfunction in chronic anoxic encephalopathy with evoked potentials].
To explore the relationship between evoked potentials (EPs) and chronic anoxic brain damage by chronic intermittent hypoxia (CIH), and provide theory evidence for diagnosis and treatment of anoxic encephalopathy. BAEP and SLSEP were recorded in rat model with CIH (hypoxia group) and rat with normoxia (normal group). Morris water maze was used to observe learning and memory ability. Immunohistochemical method was used to investigate the expression levels of caspase-3 in brain tissue. The peak latency (PL) of wave I, III, V and the interpeak latency (IPL) of wave III - V, I - V in BAEP in hypoxia group were much longer than that of in normal group (P < 0.05). The PL of wave N1, P1 of SEP in hypoxia group were much longer than that of in normal group (P < 0.05). In the water mase test, the escape latency (EL) of hypoxia group was much longer than normal group (P < 0.01). The number of caspase-3 positive cells in hypoxia group was much larger than that of in normal group (P < 0.05). There was a positive correlation among BAEP, SLSEP, the number of caspase-3 positive neuron and EL of water mase. The alteration of BAEP and SLSEP has an apparent correlation with chronic anoxic brain damage. This provides theory evidence for diagnosis and treatment of anoxic encephalopathy.


The absence of cocaine- and 6-hydroxydopamine-induced supersensitivity to oxymetazoline in the rat anococcygeus muscle.
Neither cocaine nor 6-hydroxydopamine potentiated the responses of the anococcygeus muscl_ to oxymetazoline, suggesting that the specific supersensitivity to noradrenaline produced by these drugs is due to abolition of neuronal uptake mechanisms.


Descriptive Study on Epidemiology, Clinical Presentation, Treatment, and Outcome of Supracondylar Fractures Treated in a Base Hospital of Sri Lanka: A Single-Center Study.
Supracondylar fractures are common pediatric elbow injuries, with management in developing countries presenting challenges due to limited resources, inadequate facilities, and a lack of trained personnel. This study aimed to describe the incidence, demographics, clinical presentation, treatment methods, and outcomes of supracondylar fractures treated at Ashraff Memorial Hospital (AMH)-Kalmunai, a base hospital in Sri Lanka. This is a retrospective descriptive study conducted between January 2019 and December 2020. The study involved 79 children with supracondylar fractures. The majority of the children were male (70.9%) and their ages ranged from one to 15 years. The study identified falls as the most common presenting complaint (92.4%), followed by road traffic accidents (3.8%), native treatment (2.5%), and mismanagement (1.3%). The majority of fractures affected the right side (69.6%), while the remaining cases involved the left side (30.4%). Regarding the time duration from fracture to hospital presentation, a significant proportion of children sought medical attention on the same day (51.9%), followed by presentations within the first three days (38%), within a week (5.1%), or after a month (3.8%). Based on the Gartland classification, type I fractures accounted for 44.3% of cases, followed by type II fractures (29.1%) and type III fractures (26.6%). The most common treatment approach was closed reduction and percutaneous pinning (41.8%). Other treatment options included plaster of Paris (POP) cast without manipulation (36.7%), POP cast with manipulation (7.6%), analgesics alone (6.3%), and open reduction fixation (5.1%). Follow-up procedures varied, with routine cast removal (11.4%), routine cast and K-wire removal (45.6%), and re-do surgery with routine follow-up (1.3%). Among the type III fractures, two children presented with vascular compromise and anterior interosseous nerve (AIN) impairment, while another two children had AIN impairment only. Type I and type II fractures did not exhibit nerve involvement or vascular impairment. Only one out of the 79 children had an open fracture. Supracondylar fracture is the most common orthopedic fracture in children. The study sheds light on the challenges and opportunities associated with treating pediatric supracondylar fractures in a resource-constrained context. The findings can help produce guidelines for the management of supracondylar fractures in underdeveloped nations, as well as contribute to global efforts to enhance the management of pediatric fractures.


Accumulation and speciation of Cd in Avicennia marina tissues.
Avicennia marina is a high-Cd-tolerant species in the mangrove wetlands. A hydroponic experiment was carried out to research the accumulation and chemical form distribution of Cd in the tissues of A. marina under different concentrations and durations of Cd stress. It was found that the concentrations of Cd in plant tissues followed the order of root > stem > leaf. The data suggested that root activity decreased, Cd accumulation ability weakened in roots, and the translocation factor increased in stems and leaves with the increase of stress duration. With a proactive defense mechanism, most Cd was bound to pectates, organic acids, and protein, especially in roots and stems with the most proportion of 88.51 and 78.91%, respectively, having lower biological activities. The Cd bounded to water-soluble organic acid and free inorganic aminophenol-Cd showed the lowest concentration. The pectates, organic acids, and protein-integrated Cd seem the most important in affecting Cd detoxification for A. marina; this mechanism of change in Cd biological activities decreases the toxicity of this aggressive pollutant and presents new knowledge about the tolerance of mangrove plants.


Nox NADPH oxidases and the endoplasmic reticulum.
Understanding isoform- and context-specific subcellular Nox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase compartmentalization allows relevant functional inferences. This review addresses the interplay between Nox NADPH oxidases and the endoplasmic reticulum (ER), an increasingly evident player in redox pathophysiology given its role in redox protein folding and stress responses. Catalytic/regulatory transmembrane subunits are synthesized in the ER and their processing includes folding, N-glycosylation, heme insertion, p22phox heterodimerization, as shown for phagocyte Nox2. Dual oxidase (Duox) maturation also involves the regulation by ER-resident Duoxa2. The ER is the activation site for some isoforms, typically Nox4, but potentially other isoforms. Such location influences redox/Nox-mediated calcium signaling regulation via ER targets, such as sarcoendoplasmic reticulum calcium ATPase (SERCA). Growing evidence suggests that Noxes are integral signaling elements of the unfolded protein response during ER stress, with Nox4 playing a dual prosurvival/proapoptotic role in this setting, whereas Nox2 enhances proapoptotic signaling. ER chaperones such as protein disulfide isomerase (PDI) closely interact with Noxes. PDI supports growth factor-dependent Nox1 activation and mRNA expression, as well as migration in smooth muscle cells, and PDI overexpression induces acute spontaneous Nox activation. Mechanisms of PDI effects include possible support of complex formation and RhoGTPase activation. In phagocytes, PDI supports phagocytosis, Nox activation, and redox-dependent interactions with p47phox. Together, the results implicate PDI as possible Nox organizer. We propose that convergence between Noxes and ER may have evolutive roots given ER-related functional contexts, which paved Nox evolution, namely calcium signaling and pathogen killing. Overall, the interplay between Noxes and the ER may provide relevant insights in Nox-related (patho)physiology.


Local effects of substance P on respiratory regulation in the rat medulla oblongata.
The effect of substance P (SP) and the SP antagonist [D-Pro2,D-Trp7,9]-SP on basal ventilation was investigated in halothane-anesthetized rats. Microinjections of SP (0.4-1.5 nmol) into the ventrolateral medulla oblongata (VLM), (nuclei gigantocellularis, facialis, ambiguus, and reticularis lateralis) or into the dorsomedial medulla oblongata (DM, nucleus tractus solitarius) and its ventral surroundings dose dependently increased tidal volume (VT) and/or minute ventilation. In sensitive areas, the ventilatory stimulation was initiated within minutes, peaked around 8-10 min, and slowly returned to normal over 30-45 min after the injection. In the VLM sites, the increase in VT was generally accompanied by a decrease in respiratory frequency (f), whereas in the DM, f increased in parallel with VT. Furthermore, within the VLM, the respiratory response patterns differed with the definite location of the SP injection. A shortening of inspiratory time was observed in the ventromedial part, the ventrolateral portion of the nucleus paragigantocellularis and ventral to the nucleus facialis. In contrast, a lengthening of expiratory time was seen when SP was injected or applied more laterally along the ventral portion of nucleus facialis and near or directly on the ventral medullary surface. Application of [D-Pro2, D-Trp7,9]SP before or after SP completely antagonized the excitatory effects of SP on ventilation. The SP antagonist administered into the VLM decreased the ventilatory response to hypoxic breathing but caused no change during hyperoxic conditions.


In-house intensivist presence does not affect mortality in select emergency general surgery patients.
This study aimed to assess the relationship between availability of round-the-clock (RTC) in-house intensivists and patient outcomes in people who underwent surgery for a life-threatening emergency general surgery (LT-EGS) disease such as necrotizing soft-tissue infection, ischemic enteritis, perforated viscus, and toxic colitis. Data on hospital-level critical care structures and processes from a 2015 survey of 2,811 US hospitals were linked to patient-level data from 17 State Inpatient Databases. Patients who were admitted with a primary diagnosis code for an LT-EGS disease of interest and underwent surgery on date of admission were included in analyses. We identified 3,620 unique LT-EGS admissions at 368 hospitals. At 66% (n = 243) of hospitals, 83.5% (n = 3,021) of patients were treated at hospitals with RTC intensivist-led care. These facilities were more likely to have in-house respiratory therapists and protocols to ensure availability of blood products or adherence to Surviving Sepsis Guidelines. When accounting for other key factors including overnight surgeon availability, perioperative staffing, and annual emergency general surgery case volume, not having a protocol to ensure adherence to Surviving Sepsis Guidelines (adjusted odds ratio, 2.10; 95% confidence interval, 1.12-3.94) was associated with increased odds of mortality. Our results suggest that focused treatment of sepsis along with surgical source control, rather than RTC intensivist presence, is key feature of optimizing EGS patient outcomes. Therapeutic, level III.


Effect of substituents on the excited-state dynamics of the modified DNA bases 2,4-diaminopyrimidine and 2,6-diaminopurine.
To explore the excited state dynamics of pyrimidine derivatives, we performed a combined experimental and theoretical study. We present resonant two-photon ionization (R2PI) and IR-UV double resonance spectra of 2,4-diaminopyrimidine and 2,6-diaminopurine seeded in a supersonic jet by laser desorption. For 2,4-diaminopyrimidine (S(0)-->S(1) 34,459 cm(-1)), we observed only the diamino tautomer with an excited state lifetime bracketed between experimental limits of 10 ps and 1 ns. For 2,6-diaminopurine, we observed two tautomers, the 9H- (S(0)-->S(1) 34,881 cm(-1)) and 7H- (S(0)-->S(1) 32,215 cm(-1)) diamino forms, with excited state lifetimes of 6.3±0.4 ns and 8.7±0.8 ns, respectively. We investigated the nature of the excited state of 2,4-diaminopyrimidine by means of multi-reference ab initio methods. The calculations of stationary points in the ground and excited states, minima on the S(0)/S(1) crossing seam and connecting reaction paths show that several paths with negligible barriers exist, allowing ultrafast radiationless deactivation if excited at energies slightly higher than the band origin. The sub-nanosecond lifetime found experimentally is in good agreement with this finding.


A DNAzyme sensor based on target-catalyzed hairpin assembly for enzyme-free and non-label single nucleotide polymorphism genotyping.
Single nucleotide polymorphisms (SNPs) are widely existed in human genome and associated with many diseases. Traditional PCR-based methods for SNP genotyping require protein enzyme, precise control of temperature and removal of resultant products, making the whole process labor intensive and time consuming. Although G-quadruplex DNAzyme-based assays provide many advantages over traditional approaches, the relatively low catalytic activity of DNAzyme becomes an unfavorable factor in its application process. Therefore, amplification of DNAzyme for further determination is of great desire in bioanalysis. In this work, we have developed an enzyme-free and non-label DNAzyme sensor for SNP genotyping based on target-catalyzed hairpin assembly (CHA) for DNAzyme amplification. The proposed sensor, carried out on microfluidic chemiluminescence (CL) assay, can sensitively discriminate rs242557 hotspot-SNP, the A/G single-nucleotide variation on human chromosome associated with Alzheimer's disease, with an absolute detection limit of 0.3 fmol.


Electronically excited states of protonated aromatic hydrocarbons: phenanthrene and pyrene.
The first and second electronic excited states (S1 and S2) of protonated phenanthrene and protonated pyrene, having the ππ* nature, are strongly red-shifted compared to corresponding electronic transitions in neutral homologues. The CC2 calculations identify an out-of-plane deformation as the most important photochemical reaction coordinate in protonated phenanthrene as well as protonated benzene. It was shown that the excited S1 states of protonated phenanthrene and protonated benzene are unstable via a torsional motion, which provides a fast access to a S1-S0 conical intersection. From the conical intersection, a barrier-less reaction path directs the system back to the minimum of the S0 potential-energy surface. In contrast to the most stable isomer of protonated phenanthrene, the most stable structure of protonated pyrene shows planar structure in both the S1 and S2 excited states, without considerable geometry deformations.


Stability of frozen methacholine solutions in unit-dose syringes for bronchoprovocation.
Methacholine solutions < 0.25 mg/mL must be prepared fresh daily, while concentrations > or = 0.25 mg/mL must be prepared at 2-week intervals according to US Food and Drug Administration-required labeling. The purpose of this report was to determine whether freezing methacholine solutions in unit-dose syringes would allow less frequent preparation. Diluent containing 0.5% sodium chloride, 0.275% sodium bicarbonate, and 0.4% phenol was used to prepare 11 concentrations of methacholine ranging from 0.031 to 32.0 mg/mL. Three milliliters of each dilution was placed into 5-mL polypropylene syringes and immediately frozen. Methacholine concentrations were determined using a validated high-performance liquid chromatography assay after preparation (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 5, and 6 months. On the day of analysis, the samples were allowed to thaw to room temperature. An additional set of each dilution was stored at room temperature for 24 h after thawing and then analyzed for methacholine. Samples > or = 0.062 mg/mL analyzed immediately after thawing retained > or = 90% of labeled potency for at least 6 months, while the 0.031-mg/mL sample retained 90% potency for 4 months. Most samples analyzed 24 h after thawing lost potency. If prepared and stored in unit-dose syringes frozen, methacholine solutions containing 0.062 to 32.0 mg/mL can be prepared at 6-month intervals, and solutions containing 0.031 mg/mL can be prepared at 4-month intervals. Once thawed, unused methacholine solutions should be discarded.


Pump-probe STM light emission spectroscopy for detection of photo-induced semiconductor-metal phase transition of VO2.
We attempted to observe pump-probe scanning tunneling microscopy (STM)-light emission (LE) from a VO2 thin film grown on a rutile TiO2(0 0 1) substrate, with an Ag tip fixed over a semiconducting domain. Laser pulses from a Ti:sapphire laser (wavelength 920 nm; pulse width less than 1.5 ps) irradiated the tip-sample gap as pump and probe light sources. With a photon energy of 2.7 eV, suggesting phase transition from semiconducting monoclinic (M) to metallic rutile (R) phases in relation to the electronic band structure, faint LE was observed roughly 30 ps after the irradiation of the pump pulse, followed by retention for roughly 20 ps. The incident energy fluence of the pump pulse at the gap was five orders of magnitude lower than the threshold value for reported photo-induced M-R phase transition. The mechanism that makes it possible to reduce the threshold fluence is discussed.


Clinicians' perspectives on the use of drug-eluting contact lenses for the treatment of glaucoma.
Glaucoma is the leading cause of irreversible blindness worldwide. The perspective of clinicians who treat the disease is important and may ultimately dictate the adoption of new treatment modalities, such as drug-eluting contact lenses. Recent advances have enabled contact lenses to serve as a sustained-release drug-delivery platform capable of treating glaucoma. This review covers the medical treatment of glaucoma, suboptimal adherence rates to treatment, and factors that may influence the clinical applicability of drug-eluting contact lenses. Ophthalmologists who treat glaucoma were surveyed to determine their perspective on treatment adherence, bandage contact lens use and the use of a drug-eluting contact lens to treat glaucoma. Given the challenge of treating glaucoma and the clinical need for improved drug delivery, drug-eluting contact lenses appear to be a promising treatment option.


Optical patterns with different wavelengths.
The semiconductor resonator is an example of an optical system where two modulational instabilities with different wave numbers coexist. In the limit of nascent bistability, the dynamics is generically described by a nonvariational real order parameter equation, of which we give a detailed derivation. This considerably simplifies the linear and weakly nonlinear stability analyses. When the two instabilities are close together, we derive normal form equations and put special emphasis on "envelope" branches of solutions. These particular solutions may connect the two instability points or form an isola. On the basis of these rigorous results, we finally discuss the case of distant modulational instabilities, in both one and two transverse dimensions.


Long-term follow-up of papillary and follicular thyroid carcinomas with bone metastasis.
The aims of this study were to investigate papillary and follicular thyroid carcinomas with bone metastasis in various clinical presentations and to determine the prognostic factors after multimodality treatment. A retrospective analysis was performed of 3,120 patients with papillary and follicular thyroid carcinoma. Of these patients, 131 (including 97 women, 71.8%) were diagnosed with bone metastasis and underwent follow-up at the Chang Gung Medical Center. Patients with bone metastasis were categorized into two groups. Group A was comprised of patients who were diagnosed with bone metastasis either before thyroidectomy or within 6 months of the initial thyroidectomy (90 patients, 68.7%). Group B was comprised of patients with bone metastasis who received a diagnosis 6 months post-thyroidectomy in the follow-up period (41 patients, 31.3%). After a mean follow-up period of 8.4 ± 7.0 years, there were 88 deaths (67.2%) attributed to thyroid cancer and 13 patients (9.9%) achieved disease-free status. A multivariate analysis showed that older age, early diagnosis, and brain metastasis were each associated with a poor prognosis. The difference in disease-specific mortality rates between groups A and B was significant (p < 0.0001). In conclusion, papillary and follicular thyroid cancers with bone metastasis have a high rate of mortality. Despite this high mortality, 9.9% patients still had an excellent response to treatment.


A single molecule array for digital targeted molecular analyses.
We present a new random array format together with a decoding scheme for targeted multiplex digital molecular analyses. DNA samples are analyzed using multiplex sets of padlock or selector probes that create circular DNA molecules upon target recognition. The circularized DNA molecules are amplified through rolling-circle amplification (RCA) to generate amplified single molecules (ASMs). A random array is generated by immobilizing all ASMs on a microscopy glass slide. The ASMs are identified and counted through serial hybridizations of small sets of tag probes, according to a combinatorial decoding scheme. We show that random array format permits at least 10 iterations of hybridization, imaging and dehybridization, a process required for the combinatorial decoding scheme. We further investigated the quantitative dynamic range and precision of the random array format. Finally, as a demonstration, the decoding scheme was applied for multiplex quantitative analysis of genomic loci in samples having verified copy-number variations. Of 31 analyzed loci, all but one were correctly identified and responded according to the known copy-number variations. The decoding strategy is generic in that the target can be any biomolecule which has been encoded into a DNA circle via a molecular probing reaction.


Elucidating the structural organization of a novel low-density lipoprotein nanoparticle reconstituted with docosahexaenoic acid.
Low-density lipoprotein nanoparticles reconstituted with unesterified docosahexaenoic acid (LDL-DHA) is promising nanomedicine with enhanced physicochemical stability and selective anticancer cytotoxic activity. The unique functionality of LDL-DHA ultimately relates to the structure of this nanoparticle. To date, however, little is known about the structural organization of this nanoparticle. In this study chemical, spectroscopic and electron microscopy analyses were undertaken to elucidate the structural and molecular organization of LDL-DHA nanoparticles. Unesterified DHA preferentially incorporates into the outer surface layer of LDL, where in this orientation the anionic carboxyl end of DHA is exposed to the LDL surface and imparts an electronegative charge to the nanoparticles surface. This negative surface charge promotes the monodisperse and homogeneous distribution of LDL-DHA nanoparticles in solution. Further structural analyses with cryo-electron microscopy revealed that the LDL-DHA nanostructure consist of a phospholipid bilayer surrounding an aqueous core, which is distinctly different from the phospholipid monolayer/apolar core organization of plasma LDL. Lastly, apolipoprotein B-100 remains strongly associated with this complex and maintains a discrete size and shape of the LDL-DHA nanoparticles similar to plasma LDL. This preliminary structural assessment of LDL-DHA now affords the opportunity to understand the important structure-function relationships of this novel nanoparticle.


Genetic Relationships (RAPD-PCR) Between Geographically Separated Populations of the "Cosmopolitan" Interstitial Polychaete Hesionides gohari (Hesionidae) and the Evolutionary Origin of the Freshwater Species Hesionides riegerorum.
In an analysis of the population genetics of the tiny meiofaunal polychaete Hesionides gohari, the RAPD-PCR method was applied to 49 specimens from 7 collecting sites far apart on three continents: French Atlantic coast, Mediterranean (Majorca, Giglio, Crete), Red Sea, Indian Ocean (Phuket), and U.S. Atlantic coast (Florida). In the band patterns produced with 14 arbitrary decamer primers, 496 genetic characters were detected. Genetic distances between the H. gohari populations vary between 0.55 and 0.70. The data were evaluated by three cluster programs; in the almost congruent phenograms, three clades were found with high bootstrap values: (1) European Atlantic-Mediterranean-Red Sea, (2) Indian Ocean, (3) Western Atlantic. In all cluster analyses, Hesionides riegerorum from a U.S. east coast river system is shown as genetically nearest to the Florida specimens of H. gohari, making it most probable that this freshwater species of the genus originated from a Western Atlantic H. gohari population. The genetic distances detected between the H. gohari specimens from the three continents are almost identical to those found between morphologically similar interstitial polychaete species pairs. Thus, the degree of genetic consistency is considered not to be high enough to corroborate the notion of a cosmopolitan distribution pattern, but rather suggests that the three clades represent different species.


MicroRNA-142-5p promotes the proliferation and metastasis of nasopharyngeal carcinoma.
Growing pieces of evidence reported abnormal expression of microRNA in various cancer. Our research aimed to ascertain the miR-142-5p expression and its potential function in the growth and metastasis of human nasopharyngeal carcinoma (NPC). In human NPC tissues and cell lines, miR-142-5p expression was quantified via the real-time qPCR assay. Functionally, the potential effect of miR-142-5p in human CNE-1 and SUNE-1 cells through MTT assay, colony formation assay, Transwell assay, and cell cycle assay. In addition, the potential target gene of miR-142-5p was determined by the dual-luciferase reporter assay. MiR-142-5p expression was remarkably elevated in human NPC tissues, CNE-1 and SUNE-1 cells. MiR-142-5p overexpression obviously enhanced the ability of cell proliferative and colony formation, and prevented G1 phase arrest in CNE-1 and SUNE-1 cells. Further, the migration number of NPC cells was increased compared to NP69 cells. BTG3 was identified as the direct target gene of miR-142-5p. Inhibition of BTG3 expression could reverse the cell proliferation by miR-142-5p-induced. Overall, miR-142-5p could strengthen the NPC cell's proliferation and migration by directly targeting BTG3. Hence, miR-142-5p may provide a new strategy and program for future clinical treatment of NPC.


Assessment of the hepatic arterial and portal venous blood flows during pregnancy with Doppler ultrasonography.
The aim of this study was to evaluate whether the dual hepatic blood supply is altered in healthy pregnant women compared with that in nonpregnant women. Flow wave-forms in common hepatic artery and portal vein were obtained in 67 healthy pregnant women at 10-40 weeks gestation and 22 nonpregnant women by using Doppler ultrasonography. In the nonpregnant group, the mean (SD) hepatic arterial blood flow, portal venous blood flow, and total liver blood flow were 0.57 (0.31) L/min, 1.25 (0.46) L/min, and 1.82 (0.63) L/min, respectively. In the healthy pregnant group, the portal venous blood flow and total liver blood flow significantly increased after 28 weeks gestation. However, the hepatic arterial blood flow remained unchanged during pregnancy. There was no relationship between the hepatic arterial blood flow and the portal venous blood flow. The results demonstrated that the hepatic perfusion increased during third trimester compared to nonpregnant level. Because the hepatic arterial blood flow remained unchanged during pregnancy, major determinant of the increase in the hepatic perfusion was the portal venous return. The data suggest that the hepatic arterial and portal venous vascular territories have regulatory mechanisms that allow for independent changes during pregnancy.


Photoarylation of alkenes and heteroaromatics by dibromo-BINOLs in aqueous solution.
The photochemistry of 6,6'-dibromo-BINOL (BINOL = 2,2'-dihydroxy-1,1'-binaphthyl) under mild basic conditions and its methyl and triisopropylsilyl ethers has been investigated in neat and aqueous acetonitrile through product distribution analysis and laser flash photolysis. Arylation and alkylation have been successfully achieved in the presence of allyltrimethylsilane, ethyl vinyl ether, pyrrole, pyridine, thiophene, benzene, and indole. Such a photoreactivity offers a metal and protecting group free synthetic protocol toward mono- and disubstituted 6-aryl/alkyl BINOLs, since the BINOL chirality is preserved in the photoactivation process.


Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells.
To ensure successful feeding tick saliva contains a number of inhibitory proteins that interfere with the host immune response and help to create a permissive environment for pathogen transmission. Among the potential targets of the salivary cystatins are two host cysteine proteases, cathepsin S, which is essential for antigen- and invariant chain-processing, and cathepsin C (dipeptidyl peptidase 1, DPP1), which plays a critical role in processing and activation of the granule serine proteases. Here, the effect of salivary cystatin OmC2 from Ornithodoros moubata was studied using differentiated MUTZ-3 cells as a model of immature dendritic cells of the host skin. Following internalization, cystatin OmC2 was initially found to inhibit the activity of several cysteine cathepsins, as indicated by the decreased rates of degradation of fluorogenic peptide substrates. To identify targets, affinity chromatography was used to isolate His-tagged cystatin OmC2 together with the bound proteins from MUTZ-3 cells. Cathepsins S and C were identified in these complexes by mass spectrometry and confirmed by immunoblotting. Furthermore, reduced increase in the surface expression of MHC II and CD86, which are associated with the maturation of dendritic cells, was observed. In contrast, human inhibitor cystatin C, which is normally expressed and secreted by dendritic cells, did not affect the expression of CD86. It is proposed that internalization of salivary cystatin OmC2 by the host dendritic cells targets cathepsins S and C, thereby affecting their maturation.


The effects of repeating false and misleading information on belief.
False and misleading information is readily accessible in people's environments, oftentimes reaching people repeatedly. This repeated exposure can significantly affect people's beliefs about the world, as has been noted by scholars in political science, communication, and cognitive, developmental, and social psychology. In particular, repetition increases belief in false information, even when the misinformation contradicts prior knowledge. We review work across these disciplines, identifying factors that may heighten, diminish, or have no impact on these adverse effects of repetition on belief. Specifically, we organize our discussion around variations in what information is repeated, to whom the information is repeated, how people interact with this repetition, and how people's beliefs are measured. A key cross-disciplinary theme is that the most influential factor is how carefully or critically people process the false information. However, several open questions remain when comparing findings across different fields and approaches. We conclude by noting a need for more interdisciplinary work to help resolve these questions, as well as a need for more work in naturalistic settings so that we can better understand and combat the effects of repeated circulation of false and misleading information in society. This article is categorized under: Psychology > Memory Psychology > Reasoning and Decision Making.


Humic acid degradation by the synthesized flower-like Ag/ZnO nanostructure as an efficient photocatalyst.
Nano-sized flower-like Ag/ZnO was synthesized by a simple method using zinc acetate and silver acetate under hydrothermal condition. Powder X-ray diffraction (PXRD) and transmission electron microscopy (TEM) were used to characterize the structure and morphology of the synthesized powder. Nano flower-like Ag/ZnO was used as a photocatalyst for degradation of humic acid in aqueous solution. The disappearance of HA was analyzed by measuring the absorbance of sample at special wavelength (254 nm). The effects of various parameters such as amount of photocatalyst, pH, initial humic acid concentration and irradiation time on degradation rate were systematically investigated. Photodegradation efficiency was small when the photolysis was carried out in the absence of Ag/ZnO and it was also negligible in the absence of light. Approximately 70% of humic acid (50 mg/L) has been eliminated after 40 minutes in the presences of catalyst (catalyst dose o.6 g/L and pH =7) and UVA irradiation. While, 100% of humic acid has been eliminated with solar irradiation.


Cytochemistry of the neurosecretory cells in the crab Menippe rumphii (Fabricius, Crustacea: Brachyura).
In Menippe rumphii five types of neurosecretory cells are found in the cerebral, commissural and thoracic ganglia. Detailed cytochemical observations on the neurosecretory cells revealed that they have responded strongly to saliva resistant PAS staining. Among proteins those rich in disulfides and sulhydryl groups are observed. Greater amounts of cytoplasmic RNA are observed in the reproductive season. Considerable amounts of lipids and phospholipids are also observed in the AS cells. The cytochemical differences between the NS cells and the nonsecretory neurons are also discussed.


Treatment of segmental tibial defects by bone transport with circular external fixation and a locking plate.
To evaluate the effectiveness of bone transport involving circular external fixation and locking plate application for the treatment of segmental tibial defects. A retrospective review of 12 patients with segmental tibial defects who underwent bone transport with circular external fixation and locking plate application. We evaluated external fixation time, external fixation index, time to achieve union, and complications. Clinical results were assessed using the Association for the Study and Application of the Methods of Ilizarov (ASAMI) score. Generic health-related outcome was assessed using the 36-Item Short-Form Health Survey questionnaire (SF-36). The mean follow-up was 25.8 months, and the mean defect size was 6.7 cm. All of the patients achieved union at the distraction callus and docking site. The average external fixation time was 299.5 days. The mean external fixation index was 16.5 days/cm, and the mean healing index was 44.9 days/cm. The functional outcomes were excellent in eight cases and good in four. The average SF-36 score was 92. Bone transport with external fixation and locking plate application may be a promising method for the treatment of segmental tibial defects.


Increased urinary beta 2-microglobulin after cancer chemotherapy.
The serum and urinary concentrations of beta 2-microglobulin (beta 2-m) and creatinine and the urinary concentration of albumin and IgG were measured in 14 patients with hematologic malignancies before and during chemotherapy. There was a transient increase in urinary beta 2-m in nine of the 14 patients during chemotherapy. All of the nine patients but only one of the other five patients had had recent multiple chemotherapy. The urinary beta 2-m increased in 24 courses of chemotherapy given to these nine patients and was already abnormal before 13 of these courses. The increase in urinary beta 2-m was not associated with an increase in serum beta 2-m or a significant increase in urinary albumin or IgG excretion. These results suggest that chemotherapy causes a marked transient tubular proteinuria, particularly in patients who have had previous chemotherapy.


Estrogen receptor ligands affect mitochondrial activity in SH-SY5Y human neuroblastoma cells.
We have studied the pharmacological regulation of mitochondrial activity in a human neuroblastoma cell line. Cyclosporin A was found to directly alter mitochondrial membrane potential and to decrease mitochondrial permeability as measured using calcein. The estrogen receptor ligands tamoxifen, nafoxidine and clomiphene were identified as agents which affect mitochondrial membrane potential in a cyclosporin A-like manner. Also when mitochondrial permeability was measured using calcein, tamoxifen, nafoxidine and clomiphene were effective in inhibiting dye loss from mitochondria. Nafoxidine and cyclosporin A inhibit effects of mastoparan on SH-SY5Y mitochondria. These studies indicate that estrogen receptor ligands appear to affect mitochondria in a cyclosporin A-like manner in human neuroblastoma cells.


Induced Tissue-Specific Stem Cells and Epigenetic Memory in Induced Pluripotent Stem Cells.
Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. The pattern of expressed genes, DNA methylation, and covalent histone modifications in iPS cells are very similar to those in ES cells. However, it has recently been shown that, following the reprogramming of mouse/human iPS cells, epigenetic memory is inherited from the parental cells. These findings suggest that the phenotype of iPS cells may be influenced by their cells of origin and that their skewed differentiation potential may prove useful in the generation of differentiated cell types that are currently difficult to produce from ES/iPS cells for the treatment of human diseases. Our recent study demonstrated the generation of induced tissue-specific stem (iTS) cells by transient overexpression of the reprogramming factors combined with tissue-specific selection. iTS cells are cells that inherit numerous components of epigenetic memory from donor tissue and acquire self-renewal potential. This review describes the "epigenetic memory" phenomenon in iPS and iTS cells and the possible clinical applications of these stem cells.


Novel one-dimensional polymers generated from p-Ferrocenylbenzoate: syntheses, structures, and magnetic properties.
Treatment of p-ferrocenylbenzoate [p-HOOCH4C6Fc, Fc = (eta5-C5H5)Fe(eta5-C5H5)] with Mn(OAc)2 x 2H2O or Cd(OAc)2 x 2H2O afforded one-dimensional linear chain polymer [[Mn(OOCH4C6Fc)2(mu2-OH2)(H2O)2](H2O)]n (1), double-bridge polymer [Mn(mu2-OOCH4C6Fc)2(phen)]n (phen = phenanthroline) (2), and ladderlike framework [[Cd(mu2-OOCH4C6Fc)(eta2-OOCH4C6Fc)(bbp)](CH3OH)]n (bbp = 4,4'-trimethylene-dipyridine) (3). The solution-state cyclic voltammograms indicate that the half-wave potentials of the ferrocenyl moieties in these polymers are all shifted to positive potential compared to that of sodium p-ferrocenylbenzoate. Both 1 and 2 behave as 1D Heisenberg Mn(II) chains with weak intrachain antiferromagnetic interactions between the local high-spin Mn(II) ions, and the exchange coupling parameters J (-5.20 and -3.25 cm(-1) for 1 and 2, respectively) are larger than those of most of the reported di-Mn(II) complexes that contain mu2-aqua and mu2-carboxylato units and one-dimensional Mn(II) carboxylic polymers.


The Influence of Contextual Factors on Running Performance in Female Australian Football Match-Play.
Black, GM, Gabbett, TJ, Naughton, G, Cole, MH, Johnston, RD, and Dawson, B. The influence of contextual factors on running performance in female Australian football match-play. J Strength Cond Res 33(9): 2488-2495, 2019-Given the recent growth of the professional status among multiple female football codes, the aim of this study is to investigate the effects of contextual factors on activity profiles and pacing strategies in female Australian football (AF) players. Thirty-five female AF players participated in this study. Global positioning system analysis was completed over 1 competitive season. Matches were separated into eight 10-minute periods. Greater distances were covered during the first half irrespective of playing position (effect size [ES] = 0.39-0.50, Likelihood ≥90%). Throughout a number of periods half-backs (defensive players) covered greater distances during losses (ES ≥ 0.74, Likelihood ≥92%) and against top 3 opponents (ES ≥ 1.0, Likelihood ≥97%). Midfielders and half-backs covered greater distances (ES ≥ 0.49, Likelihood ≥89%) in the final match period in winning compared with losing matches. A reduction in player work rate is evident during the second half of matches. The influence of contextual factors varied across positional groups. However, it is clear that coaches could use player rotation both early in the match in an attempt to delay the effect of fatigue and more frequently during the second half to increase running intensity.


Dissociative adsorption of 3-chloropropyne on Si(111)-(7 × 7): binding and structure.
To achieve silicon functionalization for the development of hybrid devices, multifunctional molecules may be employed to attach to the silicon surfaces. It is important to get a fundamental understanding about the molecule/silicon interface chemistry and the binding configuration. The surface chemistry of 3-chloropropyne (HC≡C-CH(2)Cl) on the Si(111)-(7 × 7) surface, as a model system for understanding the interaction of the multifunctional molecules with a silicon surface, was studied by X-ray photoelectron spectroscopy (XPS), high-resolution electron energy loss spectroscopy (HREELS), and density functional theory (DFT). The 3-chloropropyne adsorbs molecularly on the silicon surface at 110 K. A chemical reaction clearly occurs such that 3-choloropropyne bonds onto the Si(111)-(7 × 7) surface at room temperature by forming C-Si linkage through the cleavage of C-Cl bond, and preserving the ethyne C≡C triple bond. This functionalized silicon surface may act as an intermediate for the growth of multiple organic layers by further attaching other functional molecules.


[Effects of Shenmai injection on the expression of p38MAPK and the apoptosis-related genes in lung injury induced by intestinal ischemia/reperfusion in rats].
To observe the effects of Shenmai injection(SM) on p38MAPK and the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion (I/R) in rats and to investigate the protective mechanism of SM. Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery (SMA) for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: control group, intestinal ischemia/reperfusion group(I/R group), Shenmai injection treated group (SM+I/R group). Lung wet/dry weight ratio(W/D), the contents of phosphatidylcholine (PC) and total phospholipid(TPL) which are the major ingredients of pulmonary surfactant were measured, as well as the expression levels of p38MAPK, Bcl-2 and Bax proteins in lung tissue were examined by using immunohistochemical method. Compared with control group, lung W/D was significantly increased, the contents of PC and TPL were significantly decreased, the protein expression levels of p38MAPK, Bcl-2 and Bax were significantly increased in I/R group (all P<0.01). But Bax protein expression was much greater than Bcl-2 protein expression, the ratio of Bcl-2 to Bax were significantly decreased in I/R group than that in control group (P<0.01). Compared with I/R group, lung W/D was significantly decreased, while the contents of PC and TPL were significantly increased, the p38MAPK and Bax protein expression levels were significantly decreased in SM+I/R group (all P<0.01); both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SM+I/R group than those in I/R group (P<0.01). The correlation analysis indicated that the expression level of p38MAPK protein in lung tissue was negatively correlated with the contents of PC and the ratio of Bcl-2 to Bax (r is -0.787 and -0.731, all P<0.01). SM can protect the lung injury induced by intestinal I/R injury, which may be mediated by inhibiting the activation of p38MAPK, improving the ratio of Bcl-2 to Bax to inhibit lung apoptosis.


The forgotten history of signal detection theory.
Signal detection theory is one of psychology's most well-known and influential theoretical frameworks. However, the conceptual hurdles that had to be overcome before the theory could finally emerge in its modern form in the early 1950s seem to have been largely forgotten. Here, I trace the origins of signal detection theory, beginning with Fechner's (1860/1966) Elements of Psychophysics. Over and above the Gaussian-based mathematical framework conceived by Fechner in 1860, nearly a century would pass before psychophysicists finally realized in 1953 that the distribution of sensations generated by neural noise falls above, not below, the threshold of conscious awareness. An extensive body of single-unit recording and neuroimaging research conducted since then supports the idea that sensory noise yields genuinely felt conscious sensations even in the complete absence of stimulation. That hard-to-come-by insight in 1953 led immediately to the notion of a movable decision criterion and to the methodology of receiver operating characteristic (ROC) analysis. Over the ensuing years, signal detection theory and ROC analysis have had an enormous impact on basic and applied science alike. Yet, in some quarters of our field, that fact appears to be virtually unknown. By tracing both its fascinating origins and its phenomenal impact, I hope to illustrate why no area of experimental psychology should ever be oblivious to signal detection theory. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Subcutaneous reservoir placement during penile prosthesis implantation.
Currently, the prosthesis of choice for patients undergoing penile prosthesis surgery is a three piece inflatable device, as this provides optimal inflation and deflation when compared to a one or two piece prosthesis. However, prior pelvic surgery or radiation therapy can obliterate the retropubic space and make placement of the reservoir required for a three piece prosthesis difficult. We report a novel location for reservoir placement in a man who had undergone multiple pelvic surgeries after suffering a severe pelvic crush injury.


Monitoring Spontaneous Charge-Density Fluctuations by Single-Molecule Diffraction of Quantum Light.
Homodyne X-ray diffraction signals produced by classical light and classical detectors are given by the modulus square of the charge density in momentum space |σ(q)|2, missing its phase, which is required in order to invert the signal to real space. We show that quantum detection of the radiation field yields a linear diffraction pattern that reveals σ(q) itself, including the phase. We further show that repeated diffraction measurements with variable delays constitute a novel multidimensional measure of spontaneous charge-density fluctuations. Classical diffraction, in contrast, only reveals a subclass of even-order correlation functions. Simulations of two-dimensional signals obtained by two diffraction events are presented for the amino acid cysteine.


Neutrophil elastase contributes to the development of ischemia-reperfusion-induced liver injury by decreasing endothelial production of prostacyclin in rats.
We previously reported that nitric oxide (NO) derived from endothelial NO synthase (NOS) increased endothelial prostacyclin (PGI(2)) production in rats subjected to hepatic ischemia-reperfusion (I/R). The present study was undertaken to determine whether neutrophil elastase (NE) decreases endothelial production of PGI(2), thereby contributing to the development of I/R-induced liver injury by decreasing hepatic tissue blood flow in rats. Hepatic tissue levels of 6-keto-PGF(1alpha), a stable metabolite of PGI(2), were transiently increased and peaked at 1 h after reperfusion, followed by a gradual decrease until 3 h after reperfusion. Sivelestat sodium hydrochloride and L-658,758, two NE inhibitors, reduced I/R-induced liver injury. These substances inhibited the decreases in hepatic tissue levels of 6-keto-PGF(1alpha) at 2 and 3 h after reperfusion but did not affect the levels at 1 h after reperfusion. These NE inhibitors significantly increased hepatic tissue blood flow from 1 to 3 h after reperfusion. Both hepatic I/R-induced increases in the accumulation of neutrophils and the microvascular permeability were inhibited by these two NE inhibitors. Protective effects induced by the two NE inhibitors were completely reversed by pretreatment with nitro-l-arginine methyl ester, an inhibitor of NOS, or indomethacin. Administration of iloprost, a stable derivative of PGI(2), produced effects similar to those induced by NE inhibitors. These observations strongly suggest that NE might play a critical role in the development of I/R-induced liver injury by decreasing endothelial production of NO and PGI(2), leading to a decrease in hepatic tissue blood flow resulting from inhibition of vasodilation and induction of activated neutrophil-induced microvascular injury.


Perceived self-efficacy and coping styles related to stressful critical life events.
The study examined the personal resources, Self-efficacy and Coping Strategies, in a sample of pre-adolescents who experienced an emotionally and socially critical event, such as the earthquake of the 6(th) of April 2009, related to age and gender. 198 pre-adolescents, 84 girls and 114 boys (Age Mean 12 years), attending Secondary School in L'Aquila meso-seismic area. The emotional, behavioural and social capacities have been assessed with specific questionnaires administered collectively ten months after the earthquake. Multidimensional analyses produced differentiated profiles according to gender and age: self-efficacy-perception and coping strategy profiles, based on quartiles calculations, revealed the difficulties of the subjects in estimating their ability to cope with the world of relations and emotions after the critical event. The intervention could be specific to the cognitive, emotional and relational state of children and adolescents and differentiated before (prevention), during (intervention) and after the event (intervention and prevention).


Natural and semisynthetic polymers blended orodispersible films of citalopram.
This study was aimed at developing orodispersible films of citalopram using combination of natural and semisynthetic polymers for patients with swallowing problem. Okra biopolymer and moringa gum were utilized in combination with hydroxypropyl methylcellulose (HPMC) and pullulan. The disintegration time was less than 30 seconds and the drug content uniformity was 97.89-102.05% for all film formulations. Films formulated with HPMC (K15 and K4M) combination (F1) and combination of okra and HPMC K15 (F2) had superior mechanical properties as compared with F3 (okra and pullulan) and F4 (moringa gum and HPMC). Thermal analysis revealed stable formulations over the studied temperature range and the crystalline citalopram was completely or partially transformed into amorphous form as revealed by the differential thermal analysis, X-ray diffraction and scanning electron microscopy images. In conclusion, okra biopolymer could be used in combination with HPMC for the development of orodispersible films.


Pore-Scale Mechanisms for Spectral Induced Polarization of Calcite Precipitation Inferred from Geo-Electrical Millifluidics.
Spectral induced polarization (SIP) has the potential for monitoring reactive processes in the subsurface. While strong SIP responses have been measured in response to calcite precipitation, their origin and mechanism remain debated. Here we present a novel geo-electrical millifluidic setup designed to observe microscale reactive transport processes while performing SIP measurements. We induced calcite precipitation by injecting two reactive solutions into a porous medium, which led to highly localized precipitates at the mixing interface. Strikingly, the amplitude of the SIP response increased by 340% during the last 7% increase in precipitate volume. Furthermore, while the peak frequency in SIP response varied spatially over 1 order of magnitude, the crystal size range was similar along the front, contradicting assumptions in the classical grain polarization model. We argue that the SIP response of calcite precipitation in such mixing fronts is governed by Maxwell-Wagner polarization due to the establishment of a precipitate wall. Numerical simulations of the electric field suggested that spatial variation in peak frequency was related to the macroscopic shape of the front. These findings provide new insights into the SIP response of calcite precipitation and highlight the potential of geoelectrical millifluidics for understanding and modeling electrical signatures of reactive transport processes.


Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood-derived CD34+ Cells.
Platelet production occurs principally in the bone marrow in a process known as thrombopoiesis. During thrombopoiesis, hematopoietic progenitor cells differentiate to form platelet precursors called megakaryocytes, which terminally differentiate to release platelets from long cytoplasmic processes termed proplatelets. Megakaryocytes are rare cells confined to the bone marrow and are therefore difficult to harvest in sufficient numbers for laboratory use. Efficient production of human megakaryocytes can be achieved in vitro by culturing CD34+ cells under suitable conditions. The protocol detailed here describes isolation of CD34+ cells by magnetic cell sorting from umbilical cord blood samples. The necessary steps to produce highly pure, mature megakaryocytes under serum-free conditions are described. Details of phenotypic analysis of megakaryocyte differentiation and determination of proplatelet formation and platelet production are also provided. Effectors that influence megakaryocyte differentiation and/or proplatelet formation, such as anti-platelet antibodies or thrombopoietin mimetics, can be added to cultured cells to examine biological function.


Study on the nucleolar organiser regions in soft tissue liposarcoma.
The authors studied 24 cases of liposarcoma of soft tissue included in two categories: myxoid liposarcoma and pleomorphic liposarcoma. The 24 tumors were stained by Ploton's method for revealing the nucleolar organiser regions (AgNORs). AgNORs were counted in the nuclei of 100 cells/case. AgNORs in the cells of some cases showed hyperchromasia and an increased size. The results suggest a role of AgNORs as a possible prognostic discriminator of different histological types.


[Concomitant manifestation of ochronosis and chronic polyarthritis in a patient].
Ochronosis is rare disorder of tyrosin catabolism with an autosomal, recessive trait. Clinical signs predominantly affect the locomotor system. Inflammatory episodes in large joints can mimick Rheumatoid Arthritis (RA). Brownish discoloration of sclerae and cartilage is characteristic, diagnosis is confirmed by typical changes of spinal X-rays and the findings of homogentisic acid in urine samples. We describe a case of a 53 year old female patient with ochronosis and a second diagnosis of RA.


Development and Validation of an Enzymatic Method To Determine Stevioside Content from Stevia rebaudiana.
An enzymatic method for specific determination of stevioside content was established. Recombinant β-glucosidase BT_3567 (rBT_3567) from Bacteroides thetaiotaomicron HB-13 exhibited selective hydrolysis of stevioside at β-1,2-glycosidic bond to yield rubusoside and glucose. Coupling of this enzyme with glucose oxidase and peroxidase allowed for quantitation of stevioside content in Stevia samples by using a colorimetric-based approach. The series of reactions for stevioside determination can be completed within 1 h at 37 °C. Stevioside determination using the enzymatic assay strongly correlated with results obtained from HPLC quantitation (r2 = 0.9629, n = 16). The percentages of coefficient variation (CV) of within day (n = 12) and between days (n = 12) assays were lower than 5%, and accuracy ranges were 95-105%. This analysis demonstrates that the enzymatic method developed in this study is specific, easy to perform, accurate, and yields reproducible results.


Effects of positive and negative mood on sexual arousal in sexually functional males.
Effects of positive and negative musical mood induction on subjective and objective sexual arousal were examined in a group of sexually functional males (N = 24). Subjects evidenced significantly greater objective and subjective sexual response in the positive mood induction condition relative to both baseline and a neutral control condition. In contrast, the negative mood induction condition yielded significantly less objective sexual arousal than baseline and a neutral control condition. Data provide additional empirical support for the hypothesized impact of mood on sexual arousal.


BMPR-IB gene disruption causes severe limb deformities in pigs.
In an attempt to generate g.A746G substitution in the BMPR-IB gene, we unexpectedly obtained BMPR-IB homozygous knockout piglets ( BMPR-IB -/-) and heterogeneous knockout piglets with one copy of the A746G mutation ( BMPR-IB -/746G) via CRISPR/Cas9 editing. Polymerase chain reaction (PCR) and sequencing revealed complex genomic rearrangements in the target region. All BMPR-IB-disrupted piglets showed an inability to stand and walk normally. Both BMPR-IB -/- and BMPR-IB -/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms (ulna, radius) and disordered carpal, metacarpal, and phalangeal bones in the forelimbs. The piglets displayed more severe deformities in the hindlimbs by visual inspection, including fibular hemimelia, enlarged tarsal bone, and disordered toe joint bones. Limb deformities were more profound in BMPR-IB -/- piglets than in the BMPR-IB -/746G piglets. Proteomic analysis identified 139 differentially expressed proteins (DEPs) in the hindlimb fibula of BMPR -IB -/746G piglets compared to the wild-type (WT) controls. Most DEPs are involved in skeletal or embryonic development and/or the TGF-β pathway and tumor progression. Gene Ontology (GO) and protein domain enrichment analysis suggested alterations in these processes. Of the top 50 DEPs, a large proportion, e.g., C1QA, MYO1H, SRSF1, P3H1, GJA1, TCOF1, RBM10, SPP2, MMP13, and PHAX, were significantly associated with skeletal development. Our study provides novel findings on the role of BMPR-IB in mammalian limb development.


Making the connection: coupling of stress-activated ERK/MAPK (extracellular-signal-regulated kinase/mitogen-activated protein kinase) core signalling modules to extracellular stimuli and biological responses.
Signal-transduction pathways that employ members of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) family of protein Ser/Thr kinases are widely conserved among eukaryotes. The multiplicity of these pathways allows the cell to respond to divergent extracellular stimuli by initiating a broad array of responses ranging from cell growth to apoptosis. ERK/MAPK pathways are comprised of a three-tiered core-signalling module wherein ERK/MAPKs are regulated by MAPK/ERK kinases (MEKs) and MEKs, in turn, are regulated by MAPK kinase kinases (MAPKKKs). The regulation of MAPKKK-->MEK-->ERK/MAPK core-signalling modules by upstream components is poorly understood. Mammalian stress-activated ERK/MAPK pathways have been implicated in numerous important physiological functions, including inflammatory responses and apoptosis. In this review, I will discuss how mammalian stress-regulated ERK/MAPK core-signalling modules couple with members of the SPS1 family of protein kinases and to other upstream elements, and how these stress-regulated pathways influence cell function.


Treatment of primary cutaneous anaplastic large cell lymphoma.
Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare subtype of primary cutaneous lymphoma with a favorable prognosis. Primary cutaneous CD30+ lymphoproliferative disorders, which include C-ALCL and lymphomatoid papulosis, are the second most common group of cutaneous T-cell lymphomas. C-ALCL is comprised of large cells with anaplastic, pleomorphic, or immunoblastic cytomorphology, and indeed, more than 75% of the tumor cells express the CD30 antigen. C-ALCL clinically presents with solitary or localized reddish-brown nodules or tumors, and sometimes indurated papules, and they may be with ulceration covering with dark eschar. Multifocal lesions are seen in 20% of the patients. Extracutaneous dissemination, which mainly involves the regional lymph nodes, occurs in 10% of patients. A 69-year-old man noticed a mild elevated cutaneous lesion containing central ulceration covering with brownish black necrotic tissue on the right lower lip, and the lesion was surgically removed. After the first operation, another skin lesion was developed and the histological examination confirmed the diagnosis, C-ALCL. Eight specimens were excised during the 7-month follow-up period. The patient started the treatment with low-dose oral methotrexate (15 mg/wk) and there was no recurrence for 11 months.


[Tracheal laceration during intubation with a Frova introducer].
Chest trauma is the most frequent cause of tracheobronchial injury. Less common but potentially serious are lesions caused during intubation maneuvers in a difficult airway, during repeated attempts, or with stylets or other introducers. Though rare, airway lesions are life-threatening complications. We describe the case of a 46-year-old woman undergoing laparoscopic cholecystectomy whose trachea was injured during intubation with a Frova introducer. The lesion manifested with hemoptysis and subcutaneous and mediastinal emphysema early during recovery. The lesion resolved with conservative treatment and there were no sequelae.


A Review on Reinforcements and Additives in Starch-Based Composites for Food Packaging.
The research of starch as a matrix material for manufacturing biodegradable films has been gaining popularity in recent years, indicating its potential and possible limitations. To compete with conventional petroleum-based plastics, an enhancement of their low resistance to water and limited mechanical properties is essential. This review aims to discuss the various types of nanofillers and additives that have been used in plasticized starch films including nanoclays (montmorillonite, halloysite, kaolinite, etc.), poly-saccharide nanofillers (cellulose, starch, chitin, and chitosan nanomaterials), metal oxides (titanium dioxide, zinc oxide, zirconium oxide, etc.), and essential oils (carvacrol, eugenol, cinnamic acid). These reinforcements are frequently used to enhance several physical characteristics including mechanical properties, thermal stability, moisture resistance, oxygen barrier capabilities, and biodegradation rate, providing antimicrobial and antioxidant properties. This paper will provide an overview of the development of starch-based nanocomposite films and coatings applied in food packaging systems through the application of reinforcements and additives.