Reduced Tissue Response with Topical Khat Leaves after Eyelid Surgery: Preliminary Findings.
Upper eyelid blepharoplasty surgery is one of the most common plastic surgeries. Khat is used topically to reduce tissue edema. To evaluate the effect of topical khat administration after eyelid surgery on postoperative healing. Our prospective comparative study included 24 patients who underwent upper eyelid blepharoplasty or ptosis surgery between 2019 and 2020. Patients were randomly assigned to 48 hours of cold dressing with frozen khat leaves and frozen peas dressing (common practice). Postoperative photographs of the eyes were evaluated for the degree of ecchymosis and edema on postoperative days (PODs) 1, 3, and 7 by three blinded observers. Measures included tissue swelling and hemorrhage on PODs 1, 3, and 7. The mean age of the cohort was 67 ± 7 years; 17 females (71%). Khat application was associated with lower postoperative ecchymosis at each time point. Females had lower levels of postoperative ecchymosis on POD 7 (P = 0.07). Eyelid edema was more pronounced in the khat group on PODs 1 and 3, but this was reversed on POD 7. There was good agreement among all three observers in grading ecchymosis and edema (P < 0.001). The use of khat was associated with less tissue ecchymosis after oculoplastic surgery, although this was not statistically significant even following sub-population analysis. The outcome can be attributed to the active ingredients of cathinone and cathine, which cause vasoconstriction and lipolysis, and to the anti-inflammatory and anti-oxidative flavonoids and phenolic compounds. These encouraging preliminary findings warrant additional studies on a biochemical/cellular level.


Balloon dilatation and insertion of a self-expandable flexible metallic stent in a benign stricture of the left hepatic duct: case report.
A benign circumferential stenosis of the left hepatic duct was successfully treated with a self-expanding flexible metallic stent in a 70-year-old woman. Multiple intrahepatic stones were also removed percutaneously after dilatation of the tract up to a 24F diameter.


Secretion of homoarginine into the gut of chickens.
A technique, based on the homoarginine present in guanidinated proteins, has been used to distinguish between endogenous secretions and exogenous dietary amino acids in the ileal digesta of monogastric animals. This technique assumes that the ingested homoarginine is not recycled into the small intestine after absorption, but this assumption is yet to be experimentally validated in chickens. The secretion of homoarginine into the gut of broilers that were intravenously infused with 20 and 40 mmol/L homoarginine solutions was assessed. The plasma concentrations of homoarginine increased with increasing concentrations of homoarginine infused. However, only negligible levels of homoarginine (7.0 to 45.2 micrograms/g dry matter) were found in the digesta. Less than 0.01% of the intravenously infused homoarginine was recovered in the intestinal digesta, indicating that the secretion of homoarginine into the gut of chickens was insignificant.


T-lymphocyte-derived enkephalins reduce Th1/Th17 colitis and associated pain in mice.
Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4+ T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis. The anti-inflammatory effects of endogenous opioids were investigated in both Th1/Th17-associated (transfer of CD4+CD45RBhigh T lymphocytes) and Th2-associated (oxazolone) colitis models in mice. Inflammation-induced colonic damage and CD4+ T cell subsets were compared in mice treated or not treated with naloxone methiodide, a peripheral antagonist of opioid receptors. The anti-inflammatory activity of T-cell-derived enkephalins was further estimated by comparison of colitis severity in immunodeficient mice into which naïve CD4+CD45RBhigh T lymphocytes originating from wild-type or enkephalin-knockout mice had been transferred. Peripheral opioid receptor blockade increases the severity of Th1/Th17-induced colitis and attenuates Th2 oxazolone colitis. The opposite effects of naloxone methiodide treatment in these two models of intestinal inflammation are dependent on the potency of endogenous opioids to promote a Th2-type immune response. Accordingly, the transfer of enkephalin-deficient CD4+CD45RBhigh T lymphocytes into immunodeficient mice exacerbates inflammation-induced colonic injury. Endogenous opioids, including T-cell-derived enkephalins, promote a Th2-type immune response, which, depending on the context, may either attenuate (Th1/Th17-associated) or aggravate (Th2-associated) intestinal inflammation.


Results of 87 cases of intraocular lens implantation at the front of the whole capsular bag.
To prevent or delay Elschnig pearl formation, we performed an unusual surgical technique on 87 patients: intraocular lens implantation at the front of the whole capsular bag. We tried to obtain tight adhesion between the anterior and posterior capsules so the lens epithelial cells could not proliferate and form Elschnig pearls. In fact, the patients exhibited no Elschnig pearls or Soemmering's ring, but developed large anterior capsular folds and a multilayer cell membrane between both capsules after two (three cases), six (19 cases), and 12 months (14 cases). This led to a decrease in visual acuity, and a Nd:YAG laser anterior and posterior capsulotomy was required in most cases (83%). Several months later, these eyes developed enormous Elschnig pearls emanating centrifugally from the laser opening, strongly suggesting that lens epithelial cells require aqueous humor for Elschnig pearl transformation. Since it is not yet possible to obtain perfect adhesion between anterior and posterior capsules, our results confirm the need to remove the anterior capsule after extracapsular cataract extraction.


Development of environmental effects monitoring protocol in Brazil: a fish guide study of three river estuaries.
In Brazil, there are no unified and effective environmental monitoring models for bodies of water. Thus, several methodologies are used that result in information that is often difficult to compare, especially for stakeholders involved in regional water management. Studies in some countries such as Australia, Chile, the USA, and Sweden use the monitoring model implemented in Canada that was developed in the early 1990s. This model was designed to evaluate whether the current environmental regulations are sufficiently protective for pulp and paper effluents and for metal mining effluents. In this study, the Canadian Environmental Effects Monitoring methodologies were applied to three different Brazilian river basins, with the goal of constructing a framework for monitoring environmental effects. Pilot studies were carried out in the estuarine regions of the Benevente, Jucu, and Santa Maria da Vitória river basins, which are important rivers in the state of Espírito Santo. Evaluations included fish health, bioaccumulation studies, benthic invertebrate survey, and physical-chemical analyses of water and sediment. The quality of the environments was evaluated by means of seasonal samplings and comparisons between discharge, upstream, and downstream areas. This study made it possible to identify appropriate fish species to be used in environmental effects monitoring and the environmental quality of the rivers themselves as well as knowledge and policy gaps to implement such monitoring programs in Brazil. The study raises questions about the adequacy of Brazilian environmental legislation concerning tidal rivers.


A case of bipartite median nerve at the wrist.
We report a case of bipartite median nerve at the wrist associated with contracture of the flexor muscles in the forearm and anterior interosseous nerve palsy. The possibility of a bipartite median nerve must be borne in mind during operations on the distal forearm.


Immunosenescence profiles are not associated with muscle strength, physical performance and sarcopenia risk in very old adults: The Newcastle 85+ Study.
Decline in immune system function (immunosenescence) has been implicated in several age-related disorders. However, little is known about whether alteration in T-cell senescence, a process underlying immunological ageing, is related to muscle health in very old adults (aged ≥85 years). Utilising data from the Newcastle 85+ Study, we aimed to (a) derive and characterise immunosenescence profiles by clustering 13 baseline immunosenescence-related biomarkers of lymphocyte compartments in 657 participants; (b) explore the association between the profiles and 5-year change in muscle strength (grip strength) and physical performance (Timed Up-and-Go test), and (c) determine whether immunosenescence profiles predict 3-year incident sarcopenia. Two distinct clusters were identified; Cluster 1 ('Senescent-like phenotype', n = 421), and Cluster 2 ('Less senescent-like phenotype', n = 236) in individuals with complete biomarker data. Although Cluster 1 was characterised by T-cell senescence (e.g., higher frequency of CD4 and CD8 senescence-like effector memory cells), and elements of the immune risk profile (lower CD4/CD8 ratio, CMV+), it was not associated with change in muscle function over time, or with prevalent or incident sarcopenia. Future studies will determine whether more in-depth characterisation or change in T-cell phenotypes predict the decline in muscle health in late adulthood.


Crystal structure of the middle domain of human poly(A)-binding protein-interacting protein 1.
In eukaryotes, the poly(A)-binding protein (PABP) is one of the important factors for initiation of messenger RNA translation. PABP activity is regulated by the PABP-interacting proteins (Paips), which include Paip1, Paip2A, and Paip2B. Human Paip1 has three different isoforms. Here, we report the crystal structure of the middle domain of Paip1 isoform 2 (Paip1M) as determined by single-wavelength anomalous dispersion phasing. The structure reveals a crescent-shaped domain consisting of 10 α-helices and two antiparallel β-strands forming a β-hairpin. The 10 α-helices are arranged as five HEAT repeats which form a double layer of α helices with a convex and a concave surface. Despite low sequence identity, the overall fold of Paip1M is similar to the middle domain of human eIF4GII and yeast eIF4GI. Moreover, the amino-acid sequence motif and the local structure of eIF4G involved in binding of eIF4A, are conserved in Paip1. The structure reported here is the first of a member of the Paip family, thereby filling a gap in our understanding of initiation of eukaryotic mRNA translation in three dimensions.


Novel separation method for serum immunoglobulins. Application to thyroid related antibodies.
A dye-based affinity chromatographic system using Remazol yellow GGL-Sepharose is described for the fractionation of serum immunoglobulins. Immunoglobulins are sequentially eluted from the gel columns using gradients of pH and salt with greater than 88% recovery. Specific immunoglobulin activities were identified as discrete peaks and antibodies raised against the same antigen were separated. Biological properties of antibodies were retained following chromatography. The method is applicable to both human and animal immunoglobulins.


The complete genome sequence of Kineothrix sp. MB12-C1, isolated from the feces of black soldier fly larvae.
Here, we present the complete genome sequence of Kineothrix sp. MB12-C1 (= BCRC 81406), isolated from the feces of black soldier fly (Hermetia illucens) larvae. The genome of strain MB12-C1 was chosen for further species classification and comparative genomic analysis.


Highly efficient epoxidation method of olefins with hydrogen peroxide as terminal oxidant, bicarbonate as a co-catalyst and oxodiperoxo molybdenum(VI) complex as catalyst.
A combination of the newly synthesized and structurally characterized compound, [MoO(O2)2(saloxH)](saloxH2= salicylaldoxime) as catalyst, H2O2 as terminal oxidant and NaHCO3 as co-catalyst when stirred in CH3CN (10 cm3) at room temperature (rt) shows a very pronounced efficiency epoxidation of olefinic compounds, the method being green and economical.


Is ureteroscopy first line treatment for pediatric stone disease?
We report our current outcomes for ureteroscopic management of pediatric stone disease. We carried out a retrospective review of all ureteroscopic procedures for kidney or ureteral calculi performed between 2001 and 2005. Stone location and size, preoperative and postoperative stenting, intraoperative dilation, use of ureteral access sheath, stone-free rates and complications were noted. A total of 100 patients (58% female, mean age 13.2 years) underwent 115 procedures. Stones were located in the renal pelvis in 6% of patients, upper pole in 10%, mid ureter in 11%, lower pole in 17%, proximal ureter in 19% and distal ureter in 37%. Mean stone size was 8.3 mm (median 7.0), with a mean of 1.5 stones per patient. Preoperative stenting was used in 54% of patients, and a stent was placed postoperatively in 76%. Ureteral coaxial dilators and ureteral access sheaths were used in 70% and 24% of patients, respectively. There were no major intraoperative complications, although 5 patients required stent placement for ureteral perforation or extravasation. One patient had a ureteral stricture requiring ureteral reimplantation. Mean followup was 10.1 months (median 2.6). Stone-free rate was 91% on followup ultrasound, abdominal radiography or computerized tomography. Seven patients required staged ureteroscopic procedures to achieve stone-free status. While the number of percutaneous nephrolithotomy and shock wave lithotripsy cases remained stable, the number of ureteroscopic cases increased 7-fold during this period. Improved ureteroscopic access to stones throughout the pediatric urinary tract and stone-free rates that are comparable to the adult population have led to the adoption of ureteroscopy as first line therapy in children at our institution.


Neuroblastoma: paradigm for precision medicine.
Neuroblastoma (NB) is the third most common pediatric cancer. Although NB accounts for 7% of pediatric malignancies, it is responsible for more than 10% of childhood cancer-related mortality. Prognosis and treatment are determined by clinical and biological risk factors. Estimated 5-year survival rates for patients with non-high-risk and high-risk NB are more than 90% and less than 50%, respectively. Recent clinical trials have continued to reduce therapy for patients with non-high-risk NB, including the most favorable subsets who are often followed with observation approaches. In contrast, high-risk patients are treated aggressively with chemotherapy, radiation, surgery, and myeloablative and immunotherapies.


Evaluating the impacts of El Niño events on a marine bay ecosystem based on selected ecological network indicators.
El Niño events have great impacts on marine ecosystems worldwide, ranging from low trophic plankton production to fishery resources. Understanding how ecosystems respond to El Niño is the key to the success of ecosystem-based fisheries management (EBFM). However, few studies have focussed on the ecosystems respond to this natural perturbation in China seas, and the selection of effective ecological network analyses (ENA) indicators to evaluate the ecosystem response under El Niño conditions needs to be assessed. In this study, we constructed Ecopath models for Haizhou Bay in ENSO-neutral (2013) and El Niño (2015) years. Comprehensive analyses were conducted to evaluate ENA indicators in terms of sensitivity to the ecosystem variations, robustness to the model parameters uncertainties, and statistical check. Results showed that there were obvious variations in the species composition and biomass in the Haizhou Bay ecosystem under the El Niño event. Four optimal ENA indicators were selected, including total system throughput, total primary production, total system non-cycled throughflow, and ascendency. The indicators further showed a shrunken ecosystem size, increased energetic efficiency, and less organised ecosystem under the El Niño event. These findings enhance our understanding of ecosystem dynamics and underscore the need for precautionary management under El Niño conditions. Moreover, this work can be helpful in guiding the further selection of ENA indicators for evaluating and managing marine ecosystems during El Niño events elsewhere and thusly contribute to the implementation of EBFM.


The fine structure of the lateral ocellus of the dobsonfly larva.
The lateral ocelli of the dobsonfly (Protohermes grandis, Neuroptera) larva have been examined with light and electron microscopy. The larva has six ocelli on both sides of the head, each containing a single corneal lens. A conical crystalline body, of some 10-20 cells is situated immediately posterior to the lens. From 100 to 300 elongated retinular cells are arranged perpendicular to the crystalline body except at the innermost surface of the lens, where they are absent. The distal process of each retinular cell is enclosed by a tube-like rhabdom formed by the close association of microvilli from the same and adjacent distal processes. The distal process contains many mitochondria, multivesicular bodies, microtubles and pigment granules. In the dark-adapted ocellus the pigment granules are concentrated near the nucleus which lies under the rhabdomic layer. The granules diffuse toward the rhabdomic microvilli during light adaptation. Each retinular cell has a single axon, which extends from the ocellus as an ocellar nerve fiber into the optic lobe, where it frequently synapses upon second order neurons. In addition to these afferent synapses, there are two other synaptic combinations: (1) a feedback synapse from a second order neuron to a retinular axon, and (2) a synapse between second order neurons. These results suggest that photic signals reach the more proximal part of the brain via second order neurons after some degree of integration in the optic lobe.


Activation and inactivation of volume-sensitive taurine efflux from rat mammary gland.
A knowledge of volume-sensitive solute transport in mammary cells is important in light of evidence that mammary cell metabolism is regulated by the cellular hydration state. In this report we have examined volume-sensitive taurine and K+ (Rb+) transport by lactating rat mammary tissue. A hyposmotic shock increased taurine efflux from rat mammary tissue: taurine release returned to a basal level upon transferring the tissue back to an isosmotic medium. However, the time taken to activate taurine efflux was less than the time taken to inactivate taurine release. A second subsequent osmotic challenge also increased taurine release but to a lesser extent than the first osmotic shock. A similar pattern was observed for bumetanide-insensitive, volume-activated K+ (Rb+) release from mammary tissue explants suggesting that taurine and K+ efflux are acting in concert to regulate mammary cell volume. An abrupt hyposmotic shock increased taurine efflux from mammary explants to a greater extent than a gradual reduction in the osmolality of the incubation medium. Increasing extracellular K+ increased taurine release via a pathway sensitive to niflumic acid, which suggests that activation of volume-sensitive taurine efflux does not require a change in the ionic strength of the incubation medium or a decrease in intracellular osmolality. A hyposmotic shock also stimulated taurine efflux from rat mammary acini. In contrast, a hyposmotic challenge had no effect on taurine uptake measured under sodium-free conditions. Hyposmotically induced taurine efflux was not dependent upon extracellular calcium. The results suggest that taurine and K+ transport may allow mammary cells to volume-regulate and consequently help to control mammary metabolism.


Foods from black market at EU border as a neglected route of potential methicillin-resistant Staphylococcus aureus transmission.
The illegal entrance of foods to EU through black markets at the EU borders can constitute a neglected route of dissemination of foodborne pathogens, and in particular of methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have assessed the presence of MRSA in foods sold in a black market at an EU border (the southeast part of Romania, on the border with Republic of Moldavia). We performed a search for MRSA among 200 food samples collected from 2012 to 2013. All S. aureus were studied by pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility testing. MRSA isolates were further characterized by multilocus sequence typing (MLST) and SCCmec typing, and tested for the presence of Panton-Valentine leukocidin (PVL) virulence factors. Overall, 32 S. aureus isolates were recovered from 16 food samples (8%). One isolate detected in a pork lard sample was MRSA (0.5%). PFGE with the restriction enzyme SmaI revealed 12 genotypes among the 32 S. aureus isolates. The MRSA isolate belonged to sequence type 398, harbored SCCmec type V, tested negative for the presence of the PVL genes and was resistant to ciprofloxacin, tetracycline and cefazolin, besides all β-lactams. Among 31 methicillin-sensitive S. aureus (MSSA), 29% were resistant to penicillin, 9.7% to tetracycline and 3.2% to ciprofloxacin. In conclusion, in this study we report the presence of livestock-associated MRSA in foods sold in a black market at an EU border: ST398-MRSA-V. These results confirm the potential role of food in the dissemination of MRSA lineages among population, and the potential role of illegally introduced food to EU in the prevalence and evolution of MRSA clones in the community.


Conscience as a Regulatory Function: An Integrative Theory Put to the Test.
The subject of this study is an integrative theory of the conscience. According to this theory, conscience is operationalised as a regulatory function of one's own behaviour and identity, resulting from an interplay of empathy, self-conscious emotions such as guilt and shame, and moral reasoning. This study aimed to evaluate conscience in an adult forensic psychiatric sample by assessing the underlying factors proposed by Schalkwijk. Offenders (n = 48) appeared to show less affective but not less cognitive empathy, less identification with others, less personal distress in seeing others' suffering, less shame and shame-proneness, and lower levels of moral reasoning than non-offenders (n = 50). In coping with self-conscious emotions, offenders used the same amount of externalising coping strategies, but fewer internalising coping strategies.


Correction to: Two different therapies for the middle turbinate during endoscopic sinus surgery for chronic rhinosinusitis.
In the original publication of the article, Fig. 1a was missing and caption of Fig. 1a was published as caption of Fig. 1b. The correct Fig. 1 and captions are provided below.


Toward an integrative and predictive sperm quality analysis in Bos taurus.
There is a need to develop more integrative sperm quality analysis methods, enabling researchers to evaluate different parameters simultaneously cell by cell. In this work, we present a new multi-parametric fluorescent test able to discriminate different sperm subpopulations based on their labeling pattern and motility characteristics. Cryopreserved semen samples from 20 Holstein bulls were used in the study. Analyses of sperm motility using computer-assisted sperm analysis (CASA-mot), membrane integrity by acridine orange-propidium iodide combination and multi-parametric by the ISAS®3Fun kit, were performed. The new method allows a clear discrimination of sperm subpopulations based on membrane and acrosomal integrity, motility and morphology. It was also possible to observe live spermatozoa showing signs of capacitation such as hyperactivated motility and changes in acrosomal structure. Sperm subpopulation with intact plasma membrane and acrosome showed a higher proportion of motile sperm than those with damaged acrosome or increased fluorescence intensity. Spermatozoa with intact plasmalemma and damaged acrosome were static or exhibit weak movement. Significant correlations among the different sperm quality parameters evaluated were also described. We concluded that the ISAS®3Fun is an integrated method that represents an advance in sperm quality analysis with the potential to improve fertility predictions.


Tobacco control policies and youth smoking: evidence from a new era.
This chapter examines the impact of cigarette prices, taxes, and tobacco control policies on youth and young adult smoking propensity and intensity, in the U.S. during the years 1997-2001, a period characterized by significant changes in cigarette prices and tobacco control policies. Employing a fixed effects technique, we find a strong negative impact of cigarette prices and taxes on youth and young adult smoking prevalence and conditional demand. Moreover, we find purchase, use, and possession laws to be inversely related to youth and young adult smoking prevalence.


A base-stabilised arsenic(III) dication.
A bulky guanidinate ligand has been utilized in supporting a dichloroarsine, which is an excellent precursor to an arsenium cation and a 2,2'-bipyridine base stabilised arsetidinium dication.


The Keratectasia Volume (KEV) in Corneal Topography to Evaluate the Effect of Corneal Collagen Cross-linking in Pediatric Keratoconus.
The study aimed to evaluate the keratectasia volume (KEV) before and after corneal cross-linking (CXL) in pediatric patients. This study included 40 eyes of 25 pediatric patients (10-19 years) undergoing standard CXL. The support vector machine (SVM) algorithm was applied to transform mass pixels in corneal topography into a three-dimensioned model to calculate the KEV. The KEV, Kmax, K1, K2, Kave, keratectasia area (KEA), and thinnest corneal thickness (TCT) were determined before CXL and at 3, 6, and 12 months after surgery. The correlation between KEV and other parameters (Kmax, TCT, max decentration, eccentricity, and so on) was calculated. The KEV was 4.75 ± 0.74 preoperatively and 4.43 ± 1.22 postoperatively at last follow-up (p < 0.002). There was strong positive correlation between the KEV and Kmax (r = 0.806, p < 0.0005). The preoperat ive KEV was 4.32 ± 0.69 in mild to moderate keratoconus (Kmax < 58D) and 5.27 ± 0.37 in advanced keratoconus (Kmax > 58D) (p < 0.0005, t-test). Postoperative KEV and K readings remained stable at the early stage, and the KEV showed a more drastic decreasing trend than Kmax at sixth month. Statistical significance was found in the KEV between preoperative and 6 months after surgery (p < 0.0005), but not in Kmax and other parameters. In 83.3% (15 eyes out of 18 eyes) of the eyes, the preoperative KEV was greater than 4.6 in patients with significant flattening after CXL. Compared with K readings, the KEV can be regarded as a more sensitive index to evaluate the postoperative morphological changes after CXL in pediatric patients.


Catecholamine receptor sensitivity and the regulation of lipolysis in adult diabetes.
The sensitivity of alpha- and beta-adrenergic receptors, and the antilipolytic actions of prostaglandin E1 or insulin on adipose tissue of obese diabetic and non-diabetic subjects have been studied. Accumulation of cyclic AMP in adipose tissue and release of glycerol in response to several catecholamines (adrenaline, noradrenaline and isoprenaline) in the presence or absence of an alpha-adrenergic blocker (phentolamine) have been used to assess catecholamine receptor sensitivity. No differences in beta-receptor activity were observed between diabetics and non-diabetics, either on glycerol release or accumulation of cyclic AMP; alpha-receptor activity was also similar, except for significantly less accumulation of cyclic AMP in diabetic tissue incubated with noradrenaline and phentolamine (p less than 0.01). The antilipolytic action of prostaglandin E1 (at concentrations of 30 fM to 30 pM) on lipolysis (stimulated submaximally with isoprenaline, 10(-7) M) was similar in diabetic and control groups. The antilipolytic action of insulin (from 10(-10) to 10(-6) M) on lipolysis was also similar between the groups. It is concluded that neither disorders of the catecholamine receptor nor of the antiliolytic actions of prostaglandin E1 or insulin are responsible for the abnormalities of fatty acid metabolism in adult diabetes.


Discrimination of taste and preference for sweet in premature babies.
A modified method for registering non-nutritive sucking behaviour with and without taste stimulation enabled us to study taste perception of premature babies. We wanted to study how babies who had no extrauterine taste experience reacted to one or more stimuli with water and 33% glucose. Eight randomly selected healthy newborns (three of them being SGA without further symptoms), exclusively fed by gastric tube, were studied. The mean gestational age at the time of the study was 35.5 weeks. They were studied five times with water and five times with glucose just before feeding. In seven babies the sucking response to glucose was greater than that to water from the first trial onwards. Sucking response increased with repeated glucose stimulation, but remained the same with water stimulation. The eighth baby behaved completely differently. We concluded from our results that premature babies with a postconceptional age of 35 weeks can discriminate between sweet and not-sweet. The greater sucking response to glucose than to water at the first trial implies a genetic factor in the preference for sweet in humans.


Pessary for Management of Cervical Varices Complicating Pregnancy.
Cervical varices complicating pregnancy are rare but can cause significant maternal and perinatal morbidity. There is limited evidence regarding the optimal management of bleeding caused by cervical varices during pregnancy. A 38-year-old woman was admitted to the hospital at 16 weeks of gestation due to vaginal hemorrhage in the setting of cervical varices accompanied by placenta previa. A cervical pessary was placed at 21 weeks of gestation without further bleeding. Magnetic resonance imaging demonstrated variceal reduction after pessary placement, and a cesarean delivery was performed at 36 weeks of gestation without complications. Cervical pessary should be considered as conservative option to control the bleeding associated with cervical varices during pregnancy.


Incidence of peripheral neuropathy and cerebellar ataxia in chronic alcoholics.
A total of 78 chronic alcoholics were examined neurologically as well as by electroneurography, myography and posturography. Clinical signs of peripheral neuropathy were detected in 45% of these patients, with electromyographic and neurographic abnormality in 67% and 55% respectively. Clinical signs of cerebellar ataxia were found in 33% of our patients, whereas posturographic measurements of increased sway were recorded in 69%. The posturographic characteristics of cerebellar anterior lobe atrophy were observed in two-thirds of the latter patients. The severity of cerebellar-ataxia did not correlate with the degree of neuropathy. This lack of correlation is interpreted as an indication of different pathogenetic mechanisms acting on peripheral nerves and cerebellum.


Incorporation of diacids into the polyglycine II structure: model studies.
Aliphatic diacids are often incorporated into polypeptide structures in order to obtain model compounds for hormones, protein turns, etc. They are also fundamental components of many commercial polyamides. On the other hand glycine, the simplest amino acid, shows unique conformational features. In order to better understand the structure of such compounds, we have synthetized and determined the molecular structure of three models represented by the general formula CH3-CH2-CH2-NH-CO-CH2-NH-CO-(CH2)n-2-CO-NH-CH2-CO-NH-CH2-CH2-CH3, with n = 3, 4, or 6. Conformational differences have been found in the dicarboxylic moiety, whereas glycine always has the polyglycine II conformation. The -CO-(CH2)n-2-CO-segment adopts a folded conformation: SS, TGT, and SGTGS for n = 3, 4, and 6, respectively. Molecular packing is always pseudohexagonal and a network of hydrogen bonds oriented in three directions at 120 degrees is formed. The results are of interest in order to provide information about polyamides in which glycine residues are incorporated. Our results confirm the tendency of glycine residues to adopt the polyglycine II conformation in its copolymers with aliphatic compounds.


Endoplasmic reticulum stress-induced hepatic stellate cell apoptosis through calcium-mediated JNK/P38 MAPK and Calpain/Caspase-12 pathways.
Recent reports considered that it was the disturbance of calcium homeostasis and the accumulation of misfolded proteins in the endoplasmic reticulum (ER) that activated hepatic stellate cells (HSCs) apoptosis and promoted fibrosis resolution. However, the signal-transducing events that are activated by ER stress after HSCs activation were incompletely understood. In this study, we induced ER stress with thapsigargin (TG), and determined the activation of calpain and the cleavage of caspase by analyzing the protein levels and the correspondingly increased intracellular calcium levels and the induction of the proapoptotic transcription factor CHOP. Moreover, the phosphorylation of JNK and p38 MAPK were followed by the activation of the executioner caspases, caspase-3. As expected, preventing an increase in intracellular calcium levels using intracellular calcium chelators, EGTA, and BAPTA/AM, could substantially inhibit the phosphorylation of JNK and p38 MAPK, abolish the activation of calpains, namely caspase-12, caspase-9, and caspase-3, and provide significant protection for TG-treated activated HSCs. Interestingly, pretreatment with p38 MAPK inhibitor SB202190, JNK inhibitor SP600125, the pan-caspase inhibitor z-VAD-FMK, or calpain inhibitors calpeptin, significantly reduced the cell apoptosis and the cleavage of caspase-12 and caspase-3. However, pretreatment with z-VAD-FMK failed to reduce the activation of calpain. Additionally, pretreatment with SB202190 and SP600125 also decreased the expression of CHOP. Importantly, PDGF-induced collagen Col1α1 and α-smooth muscle actin (α-SMA), markers for the perpetuation phase of HSCs activation, were inhibited in TG-treated activated HSCs. These findings showed that the Calpain/Caspase-12 activation induced by ER stress and the JNK/p38 MAPK phosphorylation induced by the increase of intracellular calcium concentration releasing from ER are the novel signaling pathway underlying the molecular mechanism of fibrosis recovery.


Effects of acute smoking and exercise on high-density lipoprotein-cholesterol and subfractions in black female smokers.
This study investigated the effects of acute bouts of both exercise and smoking on high-density lipoprotein-cholesterol subfractions, HDL2-C and HDL3-C in black females. During two testing trials, seven subjects were exposed to either acute exercise or smoking. Treadmill exercise was performed at 70% of heart rate reserve for 15 minutes. Blood samples were taken before, immediately after, and 10 minutes after exercise. The smoking trial consisted of subjects smoking two cigarettes followed by 30 minutes of nonsmoking. Blood samples were taken before smoking, after each cigarette, and after two 15-minute intervals of nonsmoking. The exercise protocol resulted in a 10.8% increase in total HDL-C, primarily through an increase in the HDL2-C subfraction. The values returned to baseline within 10 minutes after exercise. Smoking one cigarette decreased total HDL-C by 10%. Neither subfraction was significantly effected by smoking; however, the HDL3-C subfraction was decreased 11% and HDL2-C subfraction was decreased 14.7% from resting values. The maximum reduction in HDL3-C subfraction occurred after the smoking of the first cigarette, while the maximum reduction in the HDL2-C subfraction occurred after the first 15-minute nonsmoking period. Acute cigarette smoking was associated with a decrease in total HDL-C that was maintained through 15 minutes of nonsmoking. It is suggested that the adverse effect on HDL-C by acute smoking is a significant contributor to coronary heart disease (CHD) risk in black females. Results further indicate that low-intensity exercise is capable of transiently increasing the total HDL-C via an increase in the anti-atherogenic HDL2-C subfraction.(ABSTRACT TRUNCATED AT 250 WORDS)


Does the Elderly's Number of Prescribed Medications across Months Matter? National Cohort versus Single-Center Cohort.
To investigate the monthly number of prescribed medication (NPM) patterns among different elderly populations and the factors associated with monthly NPM changes. This retrospective cohort study was conducted using the databases obtained from National Health Insurance Research Databases and a 2000-bed academic medical center in Taiwan (i.e., single-center cohort). We compared the monthly NPMs, demographic characteristics, disease states, and health care contacts among the National Health Insurance elderly cohorts in 2006 and 2007, and for those elderly in the national and single-center cohorts who had outpatient visits from November to October in 2006 to 2007 and 2007 to 2008, respectively. Generalized estimating equation analyses of repeated measures were performed for monthly NPMs. The average monthly NPMs among the National Health Insurance elderly cohort was 2.33 in 2006 and 4.39 in 2007, respectively. After controlling for other factors, the increment in the proportion of monthly NPMs among the older elderly patients, in certain months and for those patients with hypertension and dyslipidemia, was statistically significant among the single-center cohort but was not observed in the national elderly cohort. The proportional changes decreased significantly among patients who made visits to emergency rooms and who were hospitalized during a 1-year period. There was an incremental trend of monthly NPMs among the national cohort from 2006 to 2007. Although acute exacerbations and hospitalization might be the protecting factors of increasing monthly NPMs, more attention should be paid toward high-utilization patients with specific diseases during certain months for different elderly cohorts.


The first survey of Theileria orientalis infection in Mongolian cattle.
In the present study, we have surveyed the presence of a bovine Theileria protozoan, Theileria orientalis, in Mongolian cattle and engorging tick populations from selected provinces and districts in Mongolia. The percentages of infection in the cattle and ticks ranged from 8.8 to 66.6 and from 3.7 to 73.3, respectively, on a per district basis. The genetic diversity of T. orientalis isolates was also studied, based on the protozoan gene encoding a major piroplasm surface protein (MPSP). At least five genotypes (types 1, 3, 5, 7, and N-3) of T. orientalis were found to be circulating among the Mongolian cattle and tick populations. In particular, types 3 and N-3 were common in most of the districts examined, while a strong geographical relationship among the genotypes was not detected in the present study. This is the first epidemiological report describing the presence of T. orientalis infection in Mongolian cattle.


Electroencephalography and transcranial Doppler ultrasonography in neonatal citrullinemia.
The authors present a case of citrullinemia with a genotype of argininosuccinate synthetase (ASS1), c.380 G>A (p.R127Q)/c.380 G>A (p.R127Q), in two alleles. A 3-day-old female infant presented with status epilepticus and coma. Laboratory data showed hyperammonemia and marked lactic acidosis in the blood and cerebrospinal fluid; electroencephalography showed severely suppressed cerebral activity and focal paroxysmal volleys of slow and sharp waves (< 1Hz) over the left hemisphere. Real-time transcranial Doppler ultrasonography showed a brain edema and high peaked systolic and low diastolic flows in basal, anterior, and middle cerebral arteries; however, immediately after a blood exchange transfusion, systolic flows were lower and diastolic flows were higher. The resistance indices were significantly different (means: 0.58 vs. 0.37; p=0.01). The patient was placed on diet therapy. After six blood exchange transfusions and peritoneal dialysis, her neurologic examination results and serum ammonia and lactate values were normal. The authors found that electroencephalography and transcranial Doppler ultrasonography were useful for the diagnosis and follow-up treatment of neonatal citrullinemia.


qTGW12a, a naturally varying QTL, regulates grain weight in rice.
A stable QTL associated with rice grain type with a large effect value was found in multiple environments, and its candidate genes were verified by genetic transformation. Rice (Oryza sativa L.) grain size is critical to both yield and appearance quality. Therefore, the discovery and identification of rice grain size genes can provide pathways for the cultivation of high-yielding varieties. In the present work, 45,607 SNP markers were used to construct a high-density genetic map of rice recombinant inbred lines, and hence a total of 14 quantitative trait loci (QTLs) were detected based on the phenotypic data of grain weight, grain length and grain width under four different environments. qTGW12a and qGL12 are newly detected QTLs related to grain weight, and are located between 22.43 Mb and 22.45 Mb on chromosome 12. Gene annotation shows that the QTL region contains the LOC_Os12g36660 annotated gene, which encodes the multidrug and toxic compound extrusion (MATE) transporter. Mutations in exons and the splice site were responsible for the changes in grain type and weight. Gene knockout experiments were used to verify these results. Hence, these results provide a basis for the cloning of qTGW12a. This discovery provides new insights for studying the genetic mechanism of rice grain morphology, and reveals a promising gene to ultimately increase rice yield.


Hydroperoxide-induced nucleotide degradation and adenosine formation in isolated rat cardiomyocytes.
The effect of tert-butyl hydroperoxide (tBH) on the nucleotide level in isolated cardiomyocytes from adult rats was examined. Incubation of myocytes with the hydroperoxide resulted in loss of both ATP and NAD from mitochondria and cytosol. In contrast, only the cytosolic level of NADP was increased. The effect on myocyte content of ADP and AMP was less pronounced. A significant increase in formation and release of adenosine also occurred in tBH-exposed cells. Treatment of cardiomyocytes with tBH resulted in a progressive decline of rod-shaped and viable cells, which was accompanied by an increase in numbers of hypercontracted and round myocytes in the incubation mixture. Electron microscopic examination showed an intense contraction of the cells. In summary our results demonstrate that plasma membrane damage and hypercontraction are early manifestations of tBH-induced injury to isolated cardiomyocytes. The depletion of ATP and formation of adenosine also suggest that degradation of adenine nucleotides may contribute to the cytotoxicity caused by tBH. Possible mechanisms involved in the ATP depletion are discussed.


Genetic differences in the resistance of rats to isoprenaline-induced heart lesions.
Two strains of rats were obtained by selective breeding: the IR strain, resistant to isoprenaline-induced myocardial lesions and the IS strain, sensitive to this damage. The IR rats grew more slowly, the weight of their adipose tissue was higher and the weight of m. soleus was less than that of the IS rats. The IR rats had a higher content of triglycerides in the serum and a lower isoprenaline-stimulated lipolytic activity of adipose tissue in vitro. The basal NEFA level in the serum and its rise after the administration of isoprenaline in vivo did not differ between the strains. The IR rats had a higher content of glycogen in the heart and in the muscle. After the administration of isoprenaline the glycogen content decreased more slowly in IR rats. The findings indicate a considerable importance of the glycogen stores in the heart for the resistance of myocardium to damage.


Effect of dopamine on ventilatory response to incremental exercise in man.
We investigated whether dopamine, an inhibitory neuromodulator in the carotid body, would alter the ventilatory response typically associated with metabolic (lactic) acidosis during exercise. Six subjects performed incremental cycle ergometer exercise to exhaustion during infusions of dopamine (3 micrograms.kg-1.min-1) or saline. Ventilation and pulmonary gas exchange were computed breath-by-breath; arterialized venous blood was collected every 90 sec for measurement of lactate, potassium and blood gases. The resting ventilatory response to an isocapnic step decrease in end-tidal PO2 to 50 Torr was used as an index of carotid body drive. Dopamine diminished the hypoxic ventilatory response but had no effect on the ventilatory response during exercise. Peak lactate, potassium, and ventilation were unaffected by dopamine, and the degree of respiratory compensation for the metabolic acidosis was the same as in control experiments. Therefore, either the carotid bodies respond differently to hypoxia than to acute metabolic acidosis and/or hyperkalemia during heavy exercise, or the carotid bodies are not the sole mediators of hyperventilation above the lactate threshold.


Cost-effectiveness of real-world administration of chemotherapy and add-on Viscum album L. therapy compared to chemotherapy in the treatment of stage IV NSCLC patients.
For stage IV lung cancer patients receiving add-on Viscum album L. (VA) treatment an improved overall survival was detected. Information regarding cost-effectiveness (CE) for comparisons between chemotherapy (CTx) and CTx plus additive VA in stage IV lung cancer treatment is limited. The present study assessed the costs and cost-effectiveness of CTx plus VA (V) compared to CTx alone (C) for stage IV non-small cell lung cancer (NSCLC) patients treatment in a hospital in Germany. In the observational real-world data study, data from the Network Oncology clinical registry were utilized. Enrolled stage IV lung cancer patients received the respective therapy (C or V) in a certified German Cancer Center. Cost and cost-effectiveness analyses from the hospital's perspective were investigated on the basis of overall survival (OS) and routine financial controlling data. In addition, the incremental cost-effectiveness ratio (ICER) was calculated. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. 118 patients (C: n = 86, V: n = 32) were included in the analysis, mean age 63.8 years, the proportion of male patients was 55.1%. Adjusted hospital's total mean costs for patients from the C and V group were €16,289, 95%CI: 13,834€-18,744€ (over an adjusted mean OS time of 13.4 months) and €17,992, 95%CI: 13,658-22,326 (over an adjusted mean OS time of 19.1 months), respectively. The costs per additional OS year gained (ICER) with the V-therapy compared to C therapy were €3,586. The findings of the present study suggest that the combined use of chemotherapy and VA was clinically effective and comparably cost-effective to chemotherapy alone in our analysed patient sample from the hospital's perspective. Further randomized and prospective cost-effectiveness studies are necessary to complement our findings.


Role of glucose and insulin in the dynamic regulation of glucagon release by the perfused rat pancreas.
The effect of glucose upon the release of glucagon and insulin from the perfused rat pancreas in vitro was studied by varying both the concentration of glucose (from 3.3 to 4.6, 8.5, or 11.1 mmol/l) and the time of exposure to an elevated concentration of the sugar (5, 10 or 23 min). The results suggest that the amount of insulin released during the early period of stimulation could contribute to both the speed and extent of the inhibition in glucagon release. The rate of recovery from inhibition in the A cell, however, appeared to be independent of insulin and was related, in a dose-dependent and time-dependent manner, only to the glucose stimulus. It is suggested that a direct effect of glucose upon the A cell is involved in the physiological regulation of glucagon secretion. An indirect effect of glucose, as mediated via insulin release, may contribute to the rapidity and magnitude of inhibition in A cell secretory activity.


Platelet-Rich Plasma in Arthroscopic Rotator Cuff Repair: Clinical and Radiological Results of a Prospective Randomized Controlled Trial Study at 10-Year Follow-Up.
The aim of the study is to compare, at 10-year follow-up, the clinical and radiological outcomes of arthroscopic rotator cuff repair with or without the addition of platelet-rich plasma (PRP) over the tendon-bone interface at the end of the surgical procedure. Of 53 patients recruited in the study, and randomly divided into 2 groups (PRP = 26; control = 27), 38 were re-evaluated at least 10 years after the index procedure. The clinical evaluation was carried out through: University of California at Los Angeles (UCLA) Shoulder Score, Visual Analogue Scale (VAS), Simple Shoulder Test, Constant-Murley Score (CMS), Single Assessment Numerical Evaluation (SANE), American Shoulder and Elbow Surgeons (ASES) and isometric strength in abduction, forward flexion and external rotation. Musculoskeletal ultrasonography had been used to evaluate the integrity of the repaired cuff. A number of 38 (71%) patients (PRP = 17; control = 21) with a median age of 71 [64.75-76.50] years have been evaluated. Satisfaction at follow-up is high (90%), without statistically significant difference between the two groups. We report good and excellent clinical results in both groups (PRP vs control): CMS (81.62 [72.47-85.75] vs 77.97 [69.52-82.55] points), UCLA (34 [29.00-35.00] vs 33 [29.00-35.00] points), VAS (0.34 [0.00-1.85] vs 0.70 [0.00-2.45] cm). It was not possible to find a statistically significant difference for the variables analyzed, except for ASES and SANE. On average, 37% of the operated patients had a re-rupture at the ultrasound examination, regardless of the treatment group (P = 1.00). Compared with the previous radiological control at the 2-year follow-up, new retears occurred in 6% of the patients who received PRP treatment, whereas in the control group the percentage raises to 14% (P = .61). The clinical and radiological outcomes at the 10-year follow-up show a substantial uniformity of results between the 2 groups. The minor differences that had been observed at 2-year follow-up disappeared at long term. Patients' satisfaction is still high 10 years after surgical treatment. Level II, randomized controlled trial, treatment study.


Caregiver reports of serious injuries in children who remain at home after a child protective services investigation.
The study objectives were to examine serious injuries requiring medical attention among children who remain at home after a child welfare/child protective services (CPS) maltreatment investigation in the US and to determine whether child/caregiver characteristics and ongoing CPS involvement are related to injuries requiring medical attention. Using the National Survey of Child and Adolescent Well-being, we analyzed data on the subsample of children who remained at home (N = 3,440). A multivariate logistic regression model included child characteristics, chronic illness and disability in the child, level of CPS involvement, subsequent foster care placement, caregiver characteristics, and caregiver/family psychological variables. Injuries requiring medical attention were identified in 10.6% of the in-home population over a 15-month period, with no differences in rates by age. Children with a chronic medical condition (OR = 2.07; 95% CI, 1.20-3.58) and children with depressed caregivers (OR = 2.28; 95% CI, 1.45-3.58) were more likely to have an injury that required medical care. Older caregivers (>54 years) were less likely (OR = 0.15; 95% CI, 0.03-0.69) to have a child with an injury requiring care. Injuries were not related to further involvement with CPS after the initial maltreatment investigation. Children with chronic medical conditions who remained in their biological homes or whose caregivers were depressed were likely to experience an injury requiring medical attention. Older caregivers were less likely to report a child injury. Extending existing health policies for foster children to children who remain at home following referral to CPS may encourage more comprehensive injury prevention for this population.


Two-period linear mixed effects models to analyze clinical trials with run-in data when the primary outcome is continuous: Applications to Alzheimer's disease.
Study outcomes can be measured repeatedly based on the clinical trial protocol before randomization during what is known as the "run-in" period. However, it has not been established how best to incorporate run-in data into the primary analysis of the trial. We proposed two-period (run-in period and randomization period) linear mixed effects models to simultaneously model the run-in data and the postrandomization data. Compared with the traditional models, the two-period linear mixed effects models can increase the power up to 15% and yield similar power for both unequal randomization and equal randomization. Given that analysis of run-in data using the two-period linear mixed effects models allows more participants (unequal randomization) to be on the active treatment with similar power to that of the equal-randomization trials, it may reduce the dropout by assigning more participants to the active treatment and thus improve the efficiency of AD clinical trials.


New insights into the regulation of stomatal opening by blue light and plasma membrane H(+)-ATPase.
Uptake of CO(2), transpiration, and efflux of O(2) by plants through stomatal pores are indispensable aspects for survival, not only in terrestrial plants but other organisms as well. Stomatal opening is mediated by many environmental and endogenous signals, of which blue light is known to be the most effective signal. Recent investigations have revealed that blue light-induced stomatal opening, mediated by phototropins, is driven by activation of the plasma membrane H(+)-ATPase in guard cells. Moreover, blue light induces activation of H(+)-ATPase via phosphorylation of a penultimate threonine (Thr) in H(+)-ATPase and subsequent binding of the 14-3-3 protein to the phosphorylated H(+)-ATPase. These advances provide novel insights into the blue light-signaling pathway in plants and a regulatory mechanism of the plasma membrane H(+)-ATPase, the first transporter for transport of numerous solutes in plant cells, in response to physiological signals.


Ethnobotany and ecological perspectives on the management and use of plant species for a traditional fishing trap, southern coast of São Paulo, Brazil.
The cerco-fixo is an artisanal fishing trap widely used by traditional communities in the estuarine region of the southern coast of the state of São Paulo, Brazil. The primary goal of the study was to investigate, through ethnobotanical and ecological approaches, the use of plant species by traditional fishermen to build the cerco-fixo at Cardoso Island State Park and Cananéia Island. Ethnobotanical data were collected through interviews, direct observation, plant collection and identification, and document analysis. An ecological evaluation was also done comparing five 20 × 20 m plots in a managed area to five 20 × 20 m plots in an unmanaged area, both within arboreal sandy soil vegetation called restinga arbórea, found within the Brazilian Atlantic Forest domain. This study involved 34 fishermen living at Cardoso and Cananéia Islands. The fishermen know more than 90 Atlantic Forest plant species that can be used to build the cerco-fixo. Tree species from the family Myrtaceae were the most quoted in the interviews. With respect to the ecological evaluation, the cluster analyses showed greater heterogeneity in terms of floristic composition (i.e. greater floristic dissimilarity) within the plots of the managed area. The analyses of diversity showed a slightly higher species richness and slightly lower values for Shannon, Simpson, Hurlbert's PIE and Evenness indices in the managed area (59 species; H' = 3.28; 1/D = 10.77; E = 0.80; Hurlbert's PIE = 0.91) compared to the unmanaged area (54 species; H' = 3.39; 1/D = 20.21; E = 0.85; Hurlbert's PIE = 0.95). The Hutcheson's t test showed no significant difference between both areas' Shannon diversity indices (t: -1.04; p: 0.30). These results are attributed to the greater dominance of the palm species Euterpe edulis Mart. in the managed area (28.2% of the trees sampled at this area; n = 118), which equals twice the percentage of individuals of the same species found for the unmanaged area (14.6% of the sampled trees; n = 48). We discuss the impact of the fishermen's harvesting practices in the managed area with an emphasis on three main points: (1) the harvesting practices are likely not contributing to a decrease in diversity in the managed area; (2) the greater heterogeneity in terms of floristic composition found for the managed area may reflect a mosaic pattern created by the opening of small tree-gaps distributed across this area over the course of more than 50 years; (3) the disturbance promoted by the fishermen's harvesting practices can be compared to natural disturbances of low impact that create mosaic patterns in tropical forests. This study emphasizes the prominence of the human dimension in ecological processes and the importance of considering the perspectives of local people when discussing the conservation of the natural environments in which these people live.


Propolis ethanol extract abrogates hyperglycemia, lipotoxicity, and lowered hepatic poly (ADP-ribose) polymerase protein level in male albino rats.
Diabetes is a major cause of death worldwide and currently available allopathic drugs presents adverse side effects, thus, necessitating a continuous screening for natural products. This study therefore investigated the effects of Propolis Ethanol Extract (PEE) on blood sugar, lipid metabolism, and poly-(ADP)-ribose polymerase (PARPs) protein level of diabetic male Wistar rats. Seventy rats weighing between (150-180) g used in this study were randomized into seven (7) groups as follows: group 1 (Normal control given Olive oil), group 2 (Diabetic control given Olive oil), group 3 [Diabetic + PEE (200 mg/kg)], group 4 [Diabetic + (PEE 600 mg/kg)], group 5 [Diabetic + Glibenclamide (10 mg/kg)], group 6 [Normal + PEE (200 mg/kg)], and group 7 [Normal + PEE (600 mg/kg)]. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg in 0.1 M citrate buffer pH 4.5), while the vehicle and PEE were orally administered once daily. Treatment with PEE commenced after the confirmation of diabetes. Five rats from each group were sacrificed after the third and sixth weeks of PEE treatment. Administration of PEE significantly (P < 0.05) lowered the elevated fasting blood sugar, improves body weight, and abated lipotoxicity in the brain, heart, liver and kidney of the treated groups in a dose- and duration-dependent manners. The increased protein level of PARPs and lowered hydroxyl methyl-glutaryl CoA reductase activity were significantly reversed after PEE treatment. This study concludes that PEE might be a suitable and viable regimen against diabetic complications in rats.


Construction of BiVO4/NiCo2O4 nanosheet Z-scheme heterojunction for highly boost solar water oxidation.
The sluggish water oxidation process is a severe obstacle for solar-driven water splitting. Therefore, it is imperative to develop a suitable photocatalyst with reduced energy barrier for strong oxidation. In this study, a Z-scheme BiVO4/NiCo2O4 (BVO/NCO) heterojunction system was designed by decorating ultrathin nickel-cobalt (NiCo2O4) spinel nanosheets on BiVO4 as an efficient photocatalyst for water oxidation. The unique structure of the system significantly reduced the energy barrier and improved the oxidation ability of BiVO4 to efficiently enhance the separation and transfer of the photogenerated carriers. Thus, the photocatalyst delivered an excellent O2 evolution performance of 1640.9 μmol∙g-1∙h-1 and showed 124% improved efficiency as compared to pristine BiVO4 and a quantum efficiency of 5.39% at 400 nm for O2 evolution. Additionally, the theoretical calculations revealed that the formation of *OOH was the rate-determining step for water oxidation. The decoration with NiCo2O4 significantly reduced the energy barrier between *O and *OOH, which eventually improved the photocatalytic performance of BVO/NCO. The results hold great promise for the potential application of spinel-based materials in efficient photocatalytic O2 evolution and offer fundamental insights into the design of efficient water oxidation heterojunctions.


Noninvasive photoacoustic and fluorescent tracking of optical dye labeled T cellular activities of diseased sites at new depth.
The migration of immune cells is crucial to the immune response. Visualization of these processes has previously been limited because of the imaging depth. We developed a deep-penetrating, sensitive and high-resolution method to use fast photoacoustic tomography (PAT) to image the dynamic changes of T cells in lymph node and diseases at new depth (up to 9.5 mm). T cells labeled with NIR-797-isothiocyanate, an excellent near-infrared photoacoustic and fluorescent agent, were intravenously injected to the mice. We used fluorescence imaging to determine the location of T cells roughly and photoacoustic imaging is used to observe T-cell responses in diseased sites deeply and carefully. The dynamic changes of T cells in lymph node, acute disease (bacterial infection) and chronic disease (tumor) were observed noninvasively by photoacoustic and fluorescence imaging at different time points. T cells accumulated gradually and reached a maximum at 4 hours and declined afterwards in lymph node and bacterial infection site. At tumor model, T cells immigrated to the tumor with a maximum at 12 hours. Our study can not only provide a new observing method for immune activities tracking, but also enable continuous monitoring for therapeutic interventions.


Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer.
Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL. A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression-free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001). The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was -35°C (range, -96°C to -6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criteria for consideration of cryotherapy and brachytherapy are similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular patient subset.


Seismic evidence for subduction-induced mantle flows underneath Middle America.
Laboratory experiments and geodynamic simulations demonstrate that poloidal- and toroidal-mode mantle flows develop around subduction zones. Here, we use a new 3-D azimuthal anisotropy model constructed by full waveform inversion, to infer deep subduction-induced mantle flows underneath Middle America. At depths shallower than 150 km, poloidal-mode flow is perpendicular to the trajectory of the Middle American Trench. From 300 to 450 km depth, return flows surround the edges of the Rivera and Atlantic slabs, while escape flows are inferred through slab windows beneath Panama and central Mexico. Furthermore, at 700 km depth, the study region is dominated by the Farallon anomaly, with fast axes perpendicular to its strike, suggesting the development of lattice-preferred orientations by substantial stress. These observations provide depth-dependent seismic anisotropy for future mantle flow simulations, and call for further investigations about the deformation mechanisms and elasticity of minerals in the transition zone and uppermost lower mantle.


Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin.
This paper describes the synthesis and biological evaluation of a conjugate of the highly cytotoxic drug 2-pyrrolinodoxorubicin (p-DOX) with an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) as a water-soluble biocompatible polymer carrier, utilizing the advantageous concept of polymer-drug conjugates. The conjugate of p-DOX with HPMA copolymer (PHPMA/p-DOX) was prepared by reacting the PHPMA/DOX conjugate, where the DOX was bound via a hydrazone bond, with 4-iodobutyraldehyde. The hydrazone bond between the polymer and drug is susceptible to pH-controlled hydrolysis, enabling prolonged stability in circulation and fast p-DOX release under conditions mimicking the intracellular environment. The in vitro cytostatic activity of free p-DOX was in accordance with literature, whereas its PHPMA conjugate exhibited a 1.3- to 5-fold lower cytotoxicity, depending on the cancer cell line, when compared to the free p-DOX. This is in qualitative agreement with the data obtained for DOX and its HPMA copolymer conjugates. On mice bearing T-cell EL4 lymphoma, no tumor suppression was observed from the free p-DOX at a subtoxic dose of 0.1 mg/kg, whereas the PHPMA/p-DOX conjugate significantly inhibited the initial tumor growth at approximately equitoxic doses of 0.4 and 0.8 mg p-DOX eq/kg. However, moderately elevated doses of the p-DOX equivalent in the conjugate caused toxic effects, making accurate dosage setting essential.


Is focal chronic autoimmune thyroiditis an age-related disease? Differences in incidence and severity between Japanese and British.
The incidence of chronic lymphocytic thyroiditis in autopsy material from Japanese and British subjects was evaluated. Lymphocytic infiltration in representative thyroid sections from 1826 Japanese cases collected from four different institutions was analysed. The overall incidence of lymphocytic infiltration was significantly higher in females (22.2 per cent) than in males (13.9 per cent). In females, the incidence reached 23.2 per cent in the fourth decade and showed no increase with age thereafter. The overall incidence of lymphocytic infiltration in thyroid sections from 810 British cases was 42.5 per cent in females and 19.4 per cent in males; an increase in the incidence of thyroiditis from the sixth decade onwards was noted in British females, the figure reaching 50.0 per cent in those aged over 70 years. These findings suggest possible racial differences in susceptibility to chronic thyroiditis. The disorder is not necessarily related to age, increasing severity of disease with age being found only in British females.


Purtscher-like retinopathy associated with dermatomyositis and hemophagocytic lymphohistiocytosis.
An 11 year-old girl with progressive muscle weakness due to dermatomyositis and hemophagocytic lymphohistiocytosis in which multiple cotton exudates, venous tortuosity and flame haemorrhages are detected in the funduscopic examination, leading to the diagnosis of Purtscher-like retinopathy. Purstcher's retinopathy is a microvascular disorder with clinical signs of probable thrombotic origin. Its treatment is controversial, with systemic corticosteroids being the most widespread choice.


Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound.
Diabetes can promote a state of chronic inflammation associated with serious complications that are difficult to treat, including ulceration of the lower extremities and chronic wounds. Chronic wounds are often incurable and contribute to both a reduced quality of life for patients and an enormous burden for healthcare services. In diabetes, the inflammatory response early in wound healing is inappropriately amplified and prolonged, leading to the persistent presence in the wound of vastly elevated numbers of dysfunctional, hyperpolarised macrophages that fail to transition to a pro-healing phenotype. Recent evidence suggests that systemic chronic inflammation induces intrinsic defects in monocytes via chromatin modifications that may pre-programme monocytes to a pro-inflammatory phenotype, while the local wound environment inhibits differentiation to a pro-healing phenotype. Current understanding remains incomplete, and careful dissection of how local and systemic inflammation combine to negatively influence myeloid cell development will be key to developing effective therapies aimed at healing the diabetic wound.


Effects of shrinkage of the visual field through ageing on parking performance: a parametric manipulation of salience and relevance of contextual components.
The Master Activation model of attention (Michael, Vairet, and Fernandez, Capture attentionnelle en vision: La saillance, la pertinence, et la balance cortico-sous-corticale. In: G. A. Michael (ed), Neuroscience cognitive de l'attention visuelle [Cognitive Neuroscience of Visual Attention], Solal, Marseille, pp. 165-201, 2007; Michael, Lété, and Ducrot, Trajectories of Attentional Development: An Exploration with the Master Activation Map Model, Developmental Psychology, 49:615-631, 2013) was used to study visual attention and driving behaviours of younger and older drivers while parking a car. The salience and the relevance of elements present in the parking environment were manipulated during parking manoeuvres. Different effects on manoeuvring were observed depending on driver characteristics such as age and the extent of the field of view (FV). It was found that the presence of a relevant element, such as a pedestrian, impaired parking performance only among older drivers with a narrower FV. The distinct effects of salience and relevance suggest that they had different statuses in attentional processing of manoeuvring drivers.


From "Secret" to "Sensitive Issue": Shifting Ideas About HIV Disclosure Among Middle-Aged and Older Rural South Africans in the Era of Antiretroviral Treatment.
As HIV shifts from "death sentence" to "chronic condition," disclosure of HIV status to intimate partners and family is a significant component of both prevention and treatment adherence. While disclosure is closely considered in many studies, few examine middle-aged and older persons' (age 40+) perspectives or practices. We trace older rural South Africans' views on HIV disclosure to their partners and family members in a high prevalence community over a period of extensive antiretroviral treatment (ART) rollout. Community focus group discussions (FGD) conducted in 2013 and 2018 show shifts in older persons' thinking about HIV disclosure. Our FGD participants saw fewer negative consequences of disclosure in 2018 than in 2013, and highlighted positive outcomes including building trust (partners) as well as greater support for medication collection and adherence (family). Particularly as the epidemic ages in South Africa and globally, tracing changes in older persons' views on disclosure is an important step in developing messaging that could enhance treatment as prevention and ART adherence.


Radiological appearances following vertical banded gastroplasty.
Vertical banded gastroplasty was performed on 19 grossly obese patients. Upper gastrointestinal contrast studies were performed on all patients in the immediate post-operative period and at 3 months and 1 year in 16 and 12 patients, respectively. The immediate and long-term appearances are presented and discussed. The surgical outcome depends on pouch size, outlet diameter and staple line integrity, which are reliably demonstrated by double-contrast barium studies.


Recent perspective of antibiotics remediation: A review of the principles, mechanisms, and chemistry controlling remediation from aqueous media.
Antibiotic pollution is an ever-growing concern that affects the growth of plants and the well-being of animals and humans. Research on antibiotics remediation from aqueous media has grown over the years and previous reviews have highlighted recent advances in antibiotics remediation technologies, perspectives on antibiotics ecotoxicity, and the development of antibiotic-resistant genes. Nevertheless, the relationship between antibiotics solution chemistry, remediation technology, and the interactions between antibiotics and adsorbents at the molecular level is still elusive. Thus, this review summarizes recent literature on antibiotics remediation from aqueous media and the adsorption perspective. The review discusses the principles, mechanisms, and solution chemistry of antibiotics and how they affect remediation and the type of adsorbents used for antibiotic adsorption processes. The literature analysis revealed that: (i) Although antibiotics extraction and detection techniques have evolved from single-substrate-oriented to multi-substrates-oriented detection technologies, antibiotics pollution remains a great danger to the environment due to its trace level; (ii) Some of the most effective antibiotic remediation technologies are still at the laboratory scale. Thus, upscaling these technologies to field level will require funding, which brings in more constraints and doubts patterning to whether the technology will achieve the same performance as in the laboratory; and (iii) Adsorption technologies remain the most affordable for antibiotic remediation. However, the recent trends show more focus on developing high-end adsorbents which are expensive and sometimes less efficient compared to existing adsorbents. Thus, more research needs to focus on developing cheaper and less complex adsorbents from readily available raw materials. This review will be beneficial to stakeholders, researchers, and public health professionals for the efficient management of antibiotics for a refined decision.


Neural correlates of overvaluation and the effort to save possessions in a novel decision task: An exploratory fMRI study.
People exhibit a strong attachment to possessions, observed in behavioral economics through loss aversion using new items in the Endowment or IKEA effects and in clinical psychology through pathological trouble discarding domestic items in Hoarding Disorder. These fields rarely intersect, but both document a reticence to relinquish a possessed item, even at a cost, which is associated with feelings of loss but can include enhanced positive states as well. To demonstrate the shared properties of these loss-related ownership effects, we developed the Pretzel Decorating Task (PDT), which concurrently measures overvaluation of one's own over others' items and feelings of loss associated with losing a possession, alongside enhanced positive appraisals of one's items and an effort to save them. The PDT was piloted with 31 participants who decorated pretzels and responded to their own or others' items during functional neuroimaging (fMRI). Participants observed one item per trial (self or other) and could work to save it (high or low probability loss) before learning the fate of the item (trashed or saved). Finally, participants rated items and completed hoarding tendency scales. The hypotheses were supported, as even non-clinical participants overvalued, viewed as nicer, feared losing, and worked harder to save their items over others'-a response that correlated with hoarding tendencies and motor-motivational brain activation. Our region of interest in the nucleus accumbens (NAcc) was engaged when viewing one's own items to the extent that people worked harder to save them and was more active when their items were saved when they felt emotionally attached to possessions in real life. When their items were trashed, NAcc activity negatively correlated with trouble discarding and emotional attachments to possessions. Right anterior insula was more active when working to save one's own over others' items. Extensive motor-motivational areas were engaged when working to save one's own over others' items, including cerebellum, primary motor and somatosensory regions, and retrosplenial/parahippocampal regions-even after controlling for tapping. Our attachments to items are emotional, continuous across typical and pathological populations, and drive us to save possessions that we value.


Medical aspects of environmental pollution. Environmental incidents in the Netherlands 1980-1984.
In the Netherlands since 1980, 16 situations have been identified in which man might be exposed to environmental pollutants. This paper provides an overview of these incidents and describes how health risk assessments, public studies and provision of individual medical toxicological care are dealt with. The importance of involving general practitioners and other primary health care personnel at an early stage is stressed.


One- and two-day dosing intervals between mifepristone and misoprostol in second trimester medical termination of pregnancy--a randomized trial.
The recommended time interval between mifepristone and misoprostol in medical second trimester termination of pregnancy (TOP) has been 36-48 h. However, a more flexible interval would be of value. The aim of this investigation was to compare one- and two-day intervals in second trimester medical TOP. The main outcome measures were induction-to-abortion time and the rate of surgical evacuation. This open randomized trial included 227 women undergoing TOP between gestational weeks 13-24. Mifepristone (200 mg) was followed by misoprostol (400 mcg) after one (17-28 h) or two (41- 45 h) days. In intention-to-treat analysis, the median induction-to-abortion interval was 1h longer in the one-day group (8.5 versus 7.2 h, P = 0.038), but in per-protocol analysis, the rate of surgical evacuation was higher in the 2-day group [30/115 (25%) versus 40/112 (37%); 95% confidence interval 0.3-24.1, P = 0.044]. A subgroup analysis showed that the median induction-to-abortion interval was 3h longer in the one-day group, amongst women without previous vaginal deliveries (10.1 versus 7.6, P = 0.013) and when gestation exceeded 16 weeks (10.8 versus 7.2, P = 0.024). Both one- and two-day dosing intervals seem to be suitable for second trimester medical TOP, but women with no previous deliveries and those whose gestation exceeds 16 weeks may benefit from the longer interval. However, evaluated on the basis of surgical evacuation, the one-day interval could be supported as an option for second trimester medical TOP. Effective use of both one- and two-day dosing intervals is important when optimizing clinical service. ISRCTN09944151.


Exploring the interactive mechanism of acarbose with the amylase SusG in the starch utilization system of the human gut symbiont Bacteroides thetaiotaomicron through molecular modeling.
The α-amylase, SusG, is a principal component of the Bacteroides thetaiotaomicron (Bt) starch utilization system (Sus) used to metabolize complex starch molecules in the human gastrointestinal (GI) tract. We previously reported the non-microbicidal growth inhibition of Bt by the acarbose-mediated arrest of the Sus as a potential therapeutic strategy. Herein, we report a computational approach using density functional theory (DFT), molecular docking, and molecular dynamics (MD) simulation to explore the interactive mechanism between acarbose and SusG at the atomic level in an effort to understand how acarbose shuts down the Bt Sus. The docking analysis reveals that acarbose binds orthosterically to SusG with a binding affinity of -8.3 kcal/mol. The MD simulation provides evidence of conformational variability of acarbose at the active site of SusG and also suggests that acarbose interacts with the main catalytic residues via a general acid-base double-displacement catalytic mechanism. These results suggest that small molecule competitive inhibition against the SusG protein could impact the entire Bt Sus and eliminate or reduce the system's ability to metabolize starch. This computational strategy could serve as a potential avenue for structure-based drug design to discover other small molecules capable of inhibiting the Sus of Bt with high potency, thus providing a holistic approach for selective modulation of the GI microbiota.


The clinical presentation and outcomes of children infected with newly identified respiratory tract viruses.
Numerous emerging respiratory tract viruses have been identified as significant causes of acute upper and lower respiratory tract illness in children. Human metapneumovirus is a paramyxovirus discovered in 2001 in the Netherlands, with a seasonal occurrence and spectrum of clinical illness most similar to the closely related respiratory syncytial virus. Several new members of the corona-virus family have been identified, including the truly novel agent of severe acute respiratory syndrome and others that probably have been circulating undetected. Avian influenza strains have caused numerous outbreaks with high mortality, including children, and are potential causes of pandemic influenza. Several zoonotic paramyxoviruses, including Nipah and Hendra viruses, have emerged as occasional causes of sever outbreaks of respiratory tract illness in children and adults.


Pharmacokinetic evaluation of a selegiline pulsatile oral delivery system.
Selegiline is a selective, irreversible inhibitor of MAO-B, used in the treatment of Parkinson's disease, either alone or as an adjunct to L-DOPA. The sole recommended dosing regimen is 5 mg given in the morning and at noon with breakfast and lunch. A pulsatile oral dosage form was developed to mimic the conventional tablet release from two oral administrations separated by 4 h, to permit once-daily dosing and increase compliance. The pharmacokinetics of the pulsatile delivery system was studied in six healthy male volunteers. The plasma concentration-time profile from the pulsatile system of selegiline and metabolites is dissimilar to that obtained from the 5 mg bid administration of the conventional tablet and cannot be considered to be bioequivalent. The initial pulse of the delivery system is rapidly absorbed but to a lesser extent than the conventional regimen; the second pulse exhibits absorption which is delayed and prolonged. The decrease in the selegiline concentration may be due to the less absorptive surface of the lower GI tract which is available to the second pulse. Another reason could be the disparity between the in vitro and in vivo release profiles from the second pulse. Compartmental analysis indicates that the ratio of formation-absorption rate constant for the selegiline to N-desmethylselegiline pathway decreases from 1.57 +/- 1.04 for the first pulse to 0.61 +/- 0.54 for the second pulse of the pulsatile delivery system, suggesting that the upper portion of the GI tract has a greater capacity to convert selegiline to N-desmethylselegiline than the lower GI tract. The lack of in vivo and in vitro correlation is most likely due to site specific absorption/metabolism. Regimen has been previously shown to be a significant factor in estimating the extent of selegiline and metabolite exposure following oral administration. The inequivalence of dosing regimens of the same total daily dose may ultimately be linked to the saturability of gut wall metabolism. This phenomenon may preclude the development of novel delivery systems designed to mimic the recommended dosing regimen of the conventional Eldepryl tablet.


Phyto-Facilitated Bimetallic ZnFe2O4 Nanoparticles via Boswellia carteri: Synthesis, Characterization, and Anti-Cancer Activity.
The growing dissatisfaction with the available traditional chemotherapeutic agents has enhanced the need to develop new methods for obtaining materials with more effective and safe anti-cancer properties. Over the past few years, the usage of metallic nanoparticles has been a target for researchers of different scientific and commercial fields due to their tiny sizes, environment-friendly properties, and a wide range of applications. To overcome the obstacles of traditional physical and chemical methods for the synthesis of such nanoparticles, a new, less expensive, and eco-friendly method has been adopted using natural existing organisms as a reducing agent to mediate the synthesis of the desired metallic nanoparticles from their precursors, a process called green biosynthesis of nanoparticles. In the present study, zinc-iron bimetallic nanoparticles (ZnFe2O4) were synthesized via an aqueous extract of Boswellia carteri resin mixed with zinc acetate and iron chloride precursors, and they were tested for their anticancer activity. Various analytic methods were applied for the characterization of the phyto synthesized ZnFe2O4, and they were tested for their anticancer activity against MDA-MB-231, K562, MCF-7 cancer cell lines, and normal fibroblasts. Our results demonstrate the synthesis of cubic structured bimetallic nanoparticles ZnFe2O4 with an average diameter of 10.54 nm. MTT cytotoxicity assay demonstrates that our phyto-synthesized ZnFe2O4 nanoparticles exhibited a selective and potent anticancer activity against K562 and MDA-MB-231 cell lines with IC50 values 4.53 μM and 4.19 μM, respectively. In conclusion, our biosynthesized ZnFe2O4 nanoparticles show a promising, environmentally friendly, and low coast chemotherapeutic approach against selective cancers with a predicted low adverse side effect toward normal cells. Further, in vivo, advanced animal research should be done to execute their applicability in living organisms.


Are the anti-cyclic citrullinated peptide antibodies independent predictors of myocardial involvement in patients with active rheumatoid arthritis?
The anti-CCP antibodies are specific serological markers of RA, especially the aggressive course of joint disease. It has been postulated that the chronic inflammatory state is underlain by cardiovascular (CV) disease and that a higher level of anti-CCP antibodies is implicated in CV risk. The aim of the study was to assess: (i) the possible impact of anti-CCP antibodies on left ventricular diastolic dysfunction; and (ii) the possible differences in the effects of DASs on diastolic dysfunction. The study included 80 RA patients (70 females and 10 males) with no clinically evident CV disease, or concomitant diseases, and 80 matched healthy controls. Upon clinical and laboratory evaluation, all subjects underwent M-mode, two-dimensional and colour Doppler echocardiographic examination. Isovolumetric relaxation time (IVRT) prolongation as the first sign of diastolic dysfunction was present in 36.25% of RA patients and in 15% of control subjects. IVRT was found to correlate with anti-CCP antibody titre (r = 0.382, P = 0.002) and modified DAS including CRP [DAS-28-CRP(4v)] (r = 0.204, P = 0.039). On multivariate linear regression analysis, anti-CCP antibody titre showed significant correlation with IVRT, while the ratio of early and late transmitral wave (E/A ratio) independently correlated with age and DAS-28-CRP(4v). Anti-CCP antibody is an important marker, independently associated with impaired left ventricular relaxation and the DAS-28-CRP(4v) is a more sensitive predictor of cardiac involvement in the RA than the DAS-28 variant including the ESR.


The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation.
It has recently been shown that the lactation-induced inflammatory state in the liver of dairy cows is accompanied by activation of the nuclear factor E2-related factor 2 (Nrf2) pathway, which regulates the expression of antioxidant and cytoprotective genes and thereby protects tissues from inflammatory mediators and reactive oxygen species (ROS). The present study aimed to study whether the Nrf2 pathway is activated also in the liver of lactating sows. Transcript levels of known Nrf2 target genes, UGT1A1 (encoding glucuronosyltransferase 1 family, polypeptide A1), HO-1 (encoding heme oxygenase 1), NQO1 (encoding NAD(P)H dehydrogenase, quinone 1), GPX1 (encoding glutathione peroxidase), PRDX6 (encoding peroxiredoxin 6), TXNRD1 (encoding thioredoxin reductase 1), and SOD (encoding superoxide dismutase), in the liver are significantly elevated (between 1.7 and 3.1 fold) in lactating sows compared to non-lactating sows. The inflammatory state in the liver was evidenced by the finding that transcript levels of genes encoding acute phase proteins, namely haptoglobin (HP), fibrinogen γ (FGG), complement factor B (CFB), C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), were significantly higher (2 to 8.7 fold) in lactating compared to non-lactating sows. The results of the present study indicate that the Nrf2 pathway in the liver of sows is activated during lactation. The activation of Nrf2 pathway during lactation in sows might be interpreted as a physiologic means to counteract the inflammatory process and to protect the liver against damage induced by inflammatory signals and ROS.


The neural correlates of hedonic and eudaimonic happiness: An fMRI study.
The current study investigated the neural correlates of both hedonic and eudaimonic happiness. Seventeen students underwent fMRI while cued with written sentences describing three classes of life events: Hedonic events (HE), eudaimonic events (EE) and neutral events (NE). We asked participants to imagine and empathize with all these event types. Results showed that, compared to NE, both HE and EE activated a network involving frontal, temporal and parietal regions, as well as subcortical structures. However, in the HE/EE comparison, HE showed enhanced activity in frontal medial/middle regions and anterior cingulate cortex; by contrast, EE showed increased activity in the right precentral gyrus. Findings suggest that hedonic and eudaimonic happiness activate similar neural correlates. However, both kinds of happiness are also associated with distinctive brain areas serving distinctive functions.


Effects of porogen and cross-linking agents on improved properties of silica-supported macroporous chitosan membranes for enzyme immobilization.
A series of silica-supported macroporous chitosan membranes (CM15, CM20, and CM25) was prepared by varying the ratio of 70-230-μm-sized silica particles. These synthesized membranes were further cross-linked using different cross-linking agents for covalent immobilization of biological macromolecules especially enzymes and in this study, Bovine serum albumin and laccase. Effects of silica particle and cross-linking agents on their flow rates, surface properties, and chemical and biological properties were explored. Pore size of as-synthesized membranes was 0.1192, 0.1268, and 0.1623 μm, respectively, for CM15, CM20, and CM25. The effect of various parameters such as temperature and pH on the relative activity of both free and immobilized enzymes was studied in details. The relative enzyme activity upon immobilization was greatly enhanced several folds of its original activity. The stability of enzymes over a range of temperature and pH was significantly improved by immobilization. The optimum temperature and pH were determined to be 50 °C and pH 3, respectively, for both the free and the immobilized enzymes. The immobilized enzyme possessed good operational stability and reusability properties that support its potentiality for practical applications. Among three membranes, CM25 is confirmed to be efficient candidate due to its improved characteristics.


A review of recent advances in the novel therapeutic targets and immunotherapy for lung cancer.
Lung cancer is amongst the most pervasive malignancies having high mortality rates. It is broadly grouped into non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The concept of personalized medicine has overshadowed the conventional chemotherapy given to all patients with lung cancer. The targeted therapy is given to a particular population having specific mutations to help in the better management of lung cancer. The targeting pathways for NSCLC include the epidermal growth factor receptor, vascular endothelial growth factor receptor, MET (Mesenchymal epithelial transition factor) oncogene, Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK). SCLC targeting pathway includes Poly (ADP-ribose) polymerases (PARP) inhibitors, checkpoint kinase 1 (CHK 1) pathway, WEE1 pathway, Ataxia Telangiectasia and Rad3-related (ATR)/Ataxia telangiectasia mutated (ATM), and Delta-like canonical Notch ligand 3 (DLL-Immune checkpoint inhibitors like programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors and Cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) blockade are also utilized in the management of lung cancer. Many of the targeted therapies are still under development and require clinical trials to establish their safety and efficacy. This review summarizes the mechanism of molecular targets and immune-mediated targets, recently approved drugs, and their clinical trials for lung cancer.


Quantifying Healthcare Utilization and Delay in the Treatment of Gastric Stenosis Following Sleeve Gastrectomy.
Sleeve gastrectomy (SG) is the most common bariatric procedure performed. The incidence of gastric sleeve stenosis (GSS) is up to 4%, with a rising prevalence given increasing popularity of this surgery. GSS is best treated with pneumatic balloon dilation (PBD), but the diagnosis is not always straightforward, oftentimes leading to an extensive diagnostic workup. The aims of the current study were to quantify delay to treatment and overall healthcare utilization during this delay in patients with GSS following SG. This was a retrospective review of a prospectively collected database including patients with SG diagnosed with GSS between October 2017 and September 2020. The primary outcome was time between symptom development and treatment with PBD. Secondary outcomes included total healthcare utilization as reflected by the number and charges of imaging and emergency room (ER) visits. Forty-five patients were included in the analysis; 37 (82%) were female. The mean (± SD) time to treatment was 755 (± 713) days. The probability of receiving treatment at 1, 2, and 3 years was 37%, 62%, and 76%, respectively. The mean (± SD) abdominal CT scans, radiographs, and UGIS between symptoms and PBD were 1.3 ± 2.0, 1.2 ± 1.6, and 1.2 ± 1.0, respectively. The mean number of ER visits was 1.9 ± 2.5 (range 0-8). The average number of diagnostic non-therapeutic upper endoscopies was 1.6 ± 1.5. The mean (± SD) total charges were $16,473 ± 15,173. Patients who develop GSS following SG experience significant delay in diagnosis and management, reflected by multiple imaging studies, emergency department visits, and non-therapeutic procedures.


Characterization of lipolytic responses of isolated white adipocytes from hamsters.
1. Lipolysis by isolated white adipocytes from hamsters, as measured by glycerol production, was stimulated by corticotropin, isopropylnorepinephrine (INE), norepinephrine, or epinephrine (EPI), in a dose-dependent fashion. 2. Lipolysis was stimulated by five inhibitors of cyclic 3',5'-adenosine monophosphate phosphodiesterase: caffeine, theophylline, 1-methyl-3-isobutyl xanthine, 1-ethyl-4-(isopropylidenehydrazine)-1H-pyrazolo-(3,4,-b)-pyridine-5-carboxylic acid ethyl ester (SQ 20009), and 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956). Caffeine-stimulated lipolysis consistently attained higher rates than did hormone-stimulated lipolysis. However, when cells were stimulated by both caffeine and a hormone, lipolytic rates were consistently lower than those attained under the influence of caffeine alone. 3. Isolated white adipocytes from hamsters were sensitive to both alpha- and beta-adrenergic antagonists. The beta-adrenergic antagonist propranolol could completely inhibit norepinephrine-stimulated glycerol production. The alpha-adrenergic antagonist phentolamine, on the other hand, had a biphasic effect on the cells. At 5-10(-7) M or 5-10(-6) M, phentolamine enhanced norepinephrine-stimulated lipolysis, while concentrations higher than 5-10(-5) M caused inhibition. 4. The effects of two different concentrations of six antilipolytic agents, prostaglandin E1, nicotinic acid, phenylisopropyladenosine, 5-methylpyrazole-3-carboxylic acid, adenosine and insulin, were measured. With the exception of insulin, all of these agents showed much more potent inhibition of caffeine-stimulated lipolysis than of hormone-stimulated lipolysis. Insulin, in contrast, showed only modest inhibition of hormone-stimulated lipolysis and virtually no inhibition of caffeine-stimulated lipolysis.