Modulation of reflex responses of the anterior and posterior bellies of the digastric muscle in freely moving rats.
Chewing and licking are primarily activated by central pattern generator (CPG) neuronal circuits in the brainstem and when activated trigger repetitive rhythmic orofacial movements such as chewing, licking and swallowing. These CPGs are reported to modulate orofacial reflex responses in functions such as chewing. This study explored the modulation of reflex responses in the anterior and posterior bellies (ant-Dig and post-Dig, respectively) of the digastric muscle evoked by low-intensity trigeminal stimulation in conscious rats. The ant-Dig and post-Dig reflexes were evoked by using low-intensity electrical stimulation applied to either the right or left inferior alveolar nerve. Peak-to-peak amplitudes and onset latencies were measured. No difference was observed between threshold and onset latency for evoking ant-Dig and post-Dig reflexes, suggesting that the latter was also evoked disynaptically. The peak-to-peak amplitude of both reflexes was significantly reduced during chewing, licking and swallowing as compared to resting period and was lowest during the jaw-closing phase of chewing and licking. Onset latency was significantly largest during the jaw-closing phase. Inhibitory level was similar between the ant-Dig and post-Dig reflex responses and between the ipsilateral and contralateral sides. These results suggest that both the ant-Dig and post-Dig reflex responses were significantly inhibited, probably due to CPG activation during feeding behaviours to maintain coordination of jaw and hyoid movements and hence ensure smooth feeding mechanics.


A comparison of the knowledge and attitudes of concussion within higher and lower leagues of the community rugby union game.
The Rugby Football Union (RFU) HEADCASE initiative aims to educate coaches, referees, and players on concussion. Concussion in community rugby is under-reported. Therefore, players can play a role in concussion safety if they have adequate knowledge and safe attitudes. The study aimed to evaluate and compare the concussion knowledge and attitudes and Return to Play (RTP) of the community rugby union game. A descriptive, cross-sectional study. Participants (n = 87) were from level 4 or level 8 of the English rugby union league system. A modified Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version (RoCKAS-ST) questionnaire was distributed to semi-professional and amateur clubs to evaluate players concussion knowledge index (CKI) and concussion attitudes and behaviours index (CAI) regarding RTP. No statistically significant differences existed relating to knowledge, behaviours or attitude. Some worrying gaps in knowledge were identified. Findings show that community rugby union players are knowledgeable about concussion and have shown safe attitudes, however this doesn't always translate to safe behaviours. There are some gaps in their knowledge that must be addressed relating to coma and coherence of the athlete and in symptom recognition relating to sleep disturbances.


Prostatic adenocarcinoma of ductal origin.
Adenocarcinomas that arise from primary or secondary prostatic ducts have distinctive histopathologic features. The age of patients, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase are similar to those of patients with acinic carcinomas. Carcinomas of secondary ducts may be less responsive to endocrine manipulation and of greater malignancy than carcinomas of primary ducts. The course and survival of patients with ductal carcinomas treated conservatively are poor.


Social representations of mandatory vaccination in patients and general practitioners in Moselle, France.
Vaccine controversies affect the image of vaccination. At the end of 2014, there was a shortage of tetra- and pentavalent vaccines, although immunization obligation was being discussed. Our objective in this context was to study the social representations of mandatory vaccination in general practitioners and patients. Thirty general practitioners and 30 patients were recruited for this study based on hierarchal evocation. Each provided seven associations, which were revealed spontaneously in response to the evocation of the inductive concept: "mandatory vaccination". An order of importance and a connotation were attributed to them. These associations were classified into subthemes and themes. For each, the frequency of occurrence, the median rank of importance, and the polarity index were calculated and then compared. The image of vaccination was positive (polarity index from doctors and patients: +0.22 and +0.24, respectively). The doctors mentioned first the organization of the vaccine follow-up (21.9%). For patients, the benefits of vaccination predominated (22.38%), although these benefits were considered more important by the doctors. Doctors raised vaccine controversies more frequently than patients and were more concerned with the practical aspects of vaccination (injection, pain). The current controversies have not eroded the representations of mandatory vaccination. However, doctors are critical towards the media and vaccination policy. Patients, on the other hand, are afraid of side effects and do not have complete confidence in vaccination. Immunization obligation does not appear to be challenged by either of the two populations. To sustain immunization, our main asset remains communication and information to patients.


Distal anterior choroidal artery aneurysm associated with an arteriovenous malformation. Intraoperative localization and treatment.
Distal anterior choroidal artery aneurysms are rare. The outcome of patients with distal anterior choroidal artery aneurysms has been poor, and the treatment of such aneurysms is surgically challenging. The authors describe the case of an 8-year-old girl with a ruptured distal anterior choroidal artery aneurysm associated with an arteriovenous malformation (AVM). The patient experienced sudden onset of headache and vomiting. Computed tomography revealed an intraventricular haemorrhage, and cerebral angiography demonstrated an aneurysm arising from the distal portion of the right anterior choroidal artery. The patient also had an AVM in the ipsilateral temporal lobe fed by the branches of the middle cerebral artery. A right frontotemporal craniotomy was performed with the aid of intraoperative angiography to eliminate both the AVM and the aneurysm. Intraoperative angiography was helpful in confirming the complete removal of the AVM and in accurate localization of the small and deeply placed distal anterior choroidal artery aneurysm. Both the AVM and the aneurysm were successfully treated and the patient was discharged without any neurological deficits. This case is the youngest reported patient with a distal anterior choroidal artery aneurysm. This report is also the first to describe an association of such an aneurysm with an AVM. The etiology of the aneurysm formation in this case and surgical strategy for deeply placed vascular lesions are discussed.


Values, Preferences, and decisions in the care of children with developmental disabilities.
This study compared values placed on functions relevant to the well-being of young developmentally handicapped children by parents, community members, and clinicians. Thirty-two (32) parents of developmentally handicapped children and 32 adult community members were sampled in this study. The results are reviewed.


The value of serum creatine kinase in early diagnosis of heterotopic ossification.
Heterotopic ossification (HO) is a complication of spinal cord injury (SCI) characterized by formation of ectopic bone. Early diagnosis is critical, but available diagnostic methods have drawbacks. Serum creatine kinase may be a marker for the development and severity of HO. 18 SCI patients with diagnosed HO based on clinical findings and bone scintigraphy. Serum creatine kinase levels were taken at the time of diagnosis of HO and during subsequent etidronate therapy. Of the 14 patients with normal creatine kinase values, 13 had no evidence of HO on follow-up radiographic examination. Of the 4 patients with elevated creatine kinase, all developed radiographic signs of HO. Elevated serum creatine kinase may be associated with a more aggressive course of HO as well as resistance to etidronate therapy. Further studies are needed to determine whether creatine kinase may serve as a marker for early, active HO.


Ionic imprinted polymer - Vortex-assisted dispersive micro-solid phase extraction for inorganic arsenic speciation in rice by HPLC-ICP-MS.
This study combines ultrasound-assisted extraction and vortex-assisted dispersive micro-solid phase extraction using an ionic imprinted polymer as a selective sorbent for rapid isolation and pre-concentration of inorganic arsenic species (As(III) and As(V)) in extracts from rice samples prior to their determination by high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. All factors affecting the ultrasound assisted extraction of the species from rice (ultrasound amplitude, sonication time and sonication mode) and their selective pre-concentration by ionic imprinted polymer-based vortex-assisted dispersive micro-solid phase extraction (sorbent amount, extract pH, vortex extraction time and speed, eluting solution and vortex elution time and speed) were optimized. The analytical performance of the procedure was studied at optimum conditions: ultrasound continuous sonication at 40% amplitude for 2.0 min using 1:1 methanol/ultrapure as an extractant, 50 mg of sorbent, extract pH at 8.0, vortex loading at 1000 rpm for 1.0 min, and elution with ultrapure water by vortexing at 1000 rpm for 1.0 min, pre-concentration procedure which leads to a pre-concentration factor of 10. The limits of detection obtained for As (III) and As (V) were 0.20 and 0.41 μg kg-1, respectively, and were well below the maximum levels established by the European Union in rice and rice containing products. The method was found to be precise (intraday and interday relative standard deviations ≤ 11%) and selective. The accuracy was confirmed by analysing the ERM-BC211 (rice, As species) certified reference material, and the method was successfully applied to commercial rice samples.


Application of endobronchial ultrasound-guided transbronchial needle aspiration in the management of mediastinal and hilar lymphadenopathy without intrapulmonary mass: experience from the largest cancer center of southern China.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is useful for lung cancer diagnosis and lymph node staging. The purpose of this study was to investigate EBUS-TBNA for managing mediastinal and hilar lymphadenopathies without intrapulmonary masses. We retrospectively reviewed our EBUS-TBNA database that was obtained between August 2010 and October 2012. Mediastinal and hilar lymphadenopathies of unknown origin and in the absence of known pulmonary malignancies were included. Final diagnoses were determined by EBUS-TBNA, surgery, and/or clinical follow-up for at least 6 months. Sensitivity, specificity, accuracy, and positive and negative predictive values were determined using standard statistical methods. We identified 128 patients with mediastinal and hilar lymphadenopathies and without intrapulmonary masses. EBUS-TBNA was successfully performed to obtain samples from 161 lymph nodes and mediastinal masses. EBUS-TBNA was diagnostic for 119 of 128 patients (93.0%) for all disease categories. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of EBUS-TBNA were 89.8, 100, 100, 81.6, and 93.0%, respectively. The procedures were uneventful and there were no severe complications. EBUS-TBNA is a safe, minimally invasive approach for diagnosing mediastinal and hilar lymphadenopathies without intrapulmonary masses. It obviates the need for more invasive procedures for tissue sampling of the mediastinum and hilum.


Sexual orientation, treatment utilization, and barriers for alcohol related problems: Findings from a nationally representative sample.
Gay, lesbian, and bisexual (GLB) individuals appear to have an increased likelihood of alcohol use disorders and treatment utilization for alcohol related problems compared to heterosexual individuals. Despite this increase, treatment utilization rates among GLB individuals remain low. In an effort to address this, our paper examined whether or not GLB individuals encounter unique barriers when pursuing treatment for alcohol related problems. Using data from the National Epidemiologic Survey on Alcohol Related Conditions (NESARC), we examined service sector specific factors, some of which included (a) utilization rates, (b) self-reported treatment barriers, and (c) whether or not there were emergent differences among GLB individuals, after controlling for socio-demographic and clinical characteristics. Findings indicated that GLB individuals reported higher severity rates for alcohol use disorders when compared to heterosexual individuals, and were significantly more likely to utilize treatment services for alcohol related problems, however, not across all treatment sectors. While similar patterns were observed when examining barriers to treatment, bisexual individuals reported significantly more barriers than heterosexual and gay/lesbian individuals. These findings underscored the importance of identifying and developing interventions that addresses treatment barriers associated with alcohol use service utilization among GLB populations, and creating improved outreach and education programs to better address stigmas associated with substance use and sexuality.


Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c.
To examine the hypothesis that insulin and insulin-like growth factor I (IGF-I) attenuate endothelin-induced contraction of porcine coronary epicardial arteries in vitro. Endothelin-induced coronary vasoconstriction is mediated by two types of receptors, A (ETA) and B (ETB), resulting in calcium influx. Both insulin and IGF-I attenuate endothelin-induced calcium influx into porcine coronary artery smooth muscle. Epicardial arteries harvested from juvenile pigs were contracted with cumulative concentrations of endothelin-1 (ETA- and ETB-receptor agonist; 10(-10)-10(-6) M) or of sarafotoxin-6c (ETB-receptor agonist; 10(-11)-10(-7) M). In additional experiments, endothelin-1 or sarafotoxin-6c were added after incubation with 10(-8) M regular insulin or IGF-I. These experiments were repeated in vessels without endothelium. Contraction for each vessel was calculated relative to the response to 60 mM KCl. The maximal contractions to endothelin-1 in vessels with and without endothelium were 158 +/- 8 and 200 +/- 21%, respectively (p < 0.05 at 10(-8.5)-10(-6.5) M). Both insulin (at 10(-7)-10(-6) M) and IGF-I (at 10(-6.5)-10(-6) M) attenuated the contraction to endothelin-1 in vessels with intact endothelium, as well as in vessels without endothelium (at 10(-7) and 10(-6) M for insulin and 10(-7.5)-10(-6) M for IGF-I). The maximal contractions to sarafotoxin-6c in vessels with and without endothelium were 54 +/- 13 and 84 +/- 7%, respectively (p < 0.05 at 10(-9), 10(-8.5) and 10(-7) M). Insulin and IGF-I did not affect the response to sarafotoxin-6c in vessels with and without endothelium. Insulin and IGF-I attenuated ETA-receptor-mediated coronary contraction through an endothelium-independent mechanism. The IGF axis may serve as an endogenous modulator of endothelin-mediated vasoconstriction.


Intra-pituitary relationship of follicle stimulating hormone and luteinizing hormone during pubertal development in Atlantic bluefin tuna (Thunnus thynnus).
As part of the endeavor aiming at the domestication of Atlantic bluefin tuna (BFT; Thunnus thynnus), first sexual maturity in captivity was studied by documenting its occurrence and by characterizing the key hormones of the reproductive axis: follicle stimulating hormone (FSH) and luteinizing hormone (LH). The full length sequence encoding for the related hormone β-subunits, bftFSHβ and bftLHβ, were determined, revealing two bftFSHβ mRNA variants, differing in their 5' untranslated region. A quantitative immuno-dot-blot assay to measure pituitary FSH content in BFT was developed and validated enabling, for the first time in this species, data sets for both LH and FSH to be compared. The expression and accumulation patterns of LH in the pituitary showed a steady increase of this hormone, concomitant with fish age, reaching higher levels in adult females compared to males of the same age class. Conversely, the pituitary FSH levels were elevated only in 2Y and adult fish. The pituitary FSH to LH ratio was consistently higher (>1) in immature than in maturing or pubertal fish, resembling the situation in mammals. Nevertheless, the results suggest that a rise in the LH storage level above a minimum threshold may be an indicator of the onset of puberty in BFT females. The higher pituitary LH levels in adult females over males may further support this notion. In contrast three year-old (3Y) males were pubertal while cognate females were still immature. However, it is not yet clear whether the advanced puberty in the 3Y males was a general feature typifying wild BFT populations or was induced by the culture conditions. Future studies testing the effects of captivity and hormonal treatments on precocious maturity may allow for improved handling of this species in a controlled environment which would lead to more cost-efficient farming.


Modified high-density lipoprotein modulates aldosterone release through scavenger receptors via extra cellular signal-regulated kinase and Janus kinase-dependent pathways.
Patients with type 2 diabetes (T2D) manifest significant abnormalities in lipoprotein structure and function. The deleterious impact of oxidative and glycoxidative modifications on HDL-mediated atheroprotective, antiinflammatory, and antioxidative phenomena has been well established. However, the biological effects of modified HDL on adrenal steroidogenesis-which could reveal a pathophysiological link to the overactivity of the renin-angiotensin-aldosterone system and its adverse cardiovascular consequences often observed in T2D-are not well delineated. We studied the role of modified HDL on aldosterone release from adrenocortical carcinoma cells (NCI-H295R). In vitro modifications of native HDL were performed in the presence of glucose for glycoxidized HDL (glycoxHDL) and sodium hypochlorite for oxidized HDL. Angiotensin II (AngII)-sensitized H295R cells were treated with lipoproteins for 24 h, and supernatant was used to measure aldosterone release. Both native and modified HDL augmented the steroid release from AngII-sensitized cells, with glycoxHDL having the greatest impact. Both the modified forms of HDL induced a significant increase in scavenger receptor expression and employed protein kinase C as well as extracellular signal-regulated kinase as downstream effectors of aldosterone release. Native HDL and modified HDL required Janus kinase-2 for combating increased demand in steroidogenesis. Therefore, our data support the hypothesis that diabetes-induced modification of HDL may promote adrenocortical aldosterone secretion via different signal transduction pathways. This significant influence on multiple signaling mechanisms could be targeted for future research to implement novel therapeutic trials.


Genome-wide DNA methylation profiles in hepatocellular carcinoma.
Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). We have previously demonstrated that hypermethylation in candidate genes can be detected in plasma DNA before HCC diagnosis. To identify, with a genome-wide approach, additional genes hypermethylated in HCC that could be used for more accurate analysis of plasma DNA for early diagnosis, we analyzed tumor and adjacent nontumor tissues from 62 Taiwanese HCC cases using Illumina methylation arrays (Illumina, Inc., San Diego, CA) that screen 26,486 autosomal CpG sites. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor, compared to nontumor tissues. Array data were validated with pyrosequencing in a subset of five of these genes; correlation coefficients ranged from 0.92 to 0.97. Analysis of plasma DNA from 38 cases demonstrated that 37%-63% of cases had detectable hypermethylated DNA (≥ 5% methylation) for these five genes individually. At least one of these genes was hypermethylated in 87% of the cases, suggesting that measurement of DNA methylation in plasma samples is feasible. The panel of methylated genes indentified in the current study will be further tested in a large cohort of prospectively collected samples to determine their utility as early biomarkers of HCC.


Biosensing strategies for the detection of SARS-CoV-2 nucleic acids.
The COVID-19 pandemic had devastating effects throughout the world, producing a severe crisis in the health systems and in the economy of a long list of countries, even developed ones. Therefore, highly sensitive and selective analytical bioplatforms that allow the descentralized and fast detection of the severe acute respiratory síndrome coronavirus 2 (SARS-CoV-2), are extremely necessary. Since 2020, several reviews have been published, most of them focused on the different strategies to detect the SARS-CoV-2, either from RNA, viral proteins or host antibodies produced due to the presence of the virus. In this review, the most relevant biosensors for the detection of SARS-CoV-2 RNA are particularly addressed, with special emphasis on the discussion of the biorecognition layers and the different schemes for transducing the hybridization event.


Metastable high-entropy dual-phase alloys overcome the strength-ductility trade-off.
Metals have been mankind's most essential materials for thousands of years; however, their use is affected by ecological and economical concerns. Alloys with higher strength and ductility could alleviate some of these concerns by reducing weight and improving energy efficiency. However, most metallurgical mechanisms for increasing strength lead to ductility loss, an effect referred to as the strength-ductility trade-off. Here we present a metastability-engineering strategy in which we design nanostructured, bulk high-entropy alloys with multiple compositionally equivalent high-entropy phases. High-entropy alloys were originally proposed to benefit from phase stabilization through entropy maximization. Yet here, motivated by recent work that relaxes the strict restrictions on high-entropy alloy compositions by demonstrating the weakness of this connection, the concept is overturned. We decrease phase stability to achieve two key benefits: interface hardening due to a dual-phase microstructure (resulting from reduced thermal stability of the high-temperature phase); and transformation-induced hardening (resulting from the reduced mechanical stability of the room-temperature phase). This combines the best of two worlds: extensive hardening due to the decreased phase stability known from advanced steels and massive solid-solution strengthening of high-entropy alloys. In our transformation-induced plasticity-assisted, dual-phase high-entropy alloy (TRIP-DP-HEA), these two contributions lead respectively to enhanced trans-grain and inter-grain slip resistance, and hence, increased strength. Moreover, the increased strain hardening capacity that is enabled by dislocation hardening of the stable phase and transformation-induced hardening of the metastable phase produces increased ductility. This combined increase in strength and ductility distinguishes the TRIP-DP-HEA alloy from other recently developed structural materials. This metastability-engineering strategy should thus usefully guide design in the near-infinite compositional space of high-entropy alloys.


Optical recording of membrane potential responses from early embryonic chick ganglia using voltage-sensitive dyes.
Changes in absorbance of voltage-sensitive merocyanine-rhodanine dyes were used to monitor electrical responses in the semilunar ganglion of 4-10-day-old developing chick embryos. The electrical responses were simultaneously recorded from many positions in the ganglion. Stimulation of the afferent nerve fibers (the ophthalmic division of cranial nerve V) with a suction electrode led to changes in light absorption of the stained ganglia. With both the depolarizing and hyperpolarizing pulses, the change was largest at 700 nm and was eliminated at a wavelength of 620 nm where the voltage-dependent absorption change of the dyes disappears. In the 4-10-day-old embryonic ganglia, two types of optical membrane potential responses, 'non-conducted' and 'conducted' responses, were identified. The non-conducted response varied with the intensity of the stimulus and had the nature of an electrotonic spread. Furthermore, this non-conducted response exhibited an 'initial upstroke-response' followed by the steady-state plateau evoked by larger depolarizing pulses. The conducted responses were blocked by tetrodotoxin (TTX) or by high external potassium concentration. The incidence of the conducted responses increased as development proceeded from the 5th to the 10th day of age. Thus, the TTX-sensitive action potential activity is probably generated initially in the semilunar ganglion during the 5-10-day-stage of development. These data represent the first demonstration of membrane potential responses in early embryonic intact nervous system. Furthermore, these studies demonstrate the usefulness of voltage-sensitive dyes in the analysis of the organizing process of embryonic neuronal functions during these early stages of development.


PcTrim prevents early infection with white spot syndrome virus by inhibiting AP1-induced endocytosis.
Viruses have evolved various strategies to achieve early infection by initiating transcription of their own early genes via host transcription factors, such as NF-κb, STAT, and AP1. How the host copes with this immune escape has been a topic of interest. Tripartite motif (TRIM) family proteins with RING-type domains have E3 ubiquitin ligase activity and are known as host restriction factors. Trim has been reported to be associated with phagocytosis and is also believed to be involved in the activation of autophagy. Preventing the virus from entering the host cell may be the most economical way for the host to resist virus infection. The role of TRIM in the early stage of virus infection in host cells remains to be further interpreted. In the current study, a crayfish TRIM with a RING-type domain, designated as PcTrim, was significantly upregulated under white spot syndrome virus (WSSV) infection in the red swamp crayfish (Procambarus clarkii). Recombinant PcTrim significantly inhibited WSSV replication in crayfish. RNAi targeting PcTrim or blocking PcTrim with an antibody promoted WSSV replication in crayfish. Pulldown and co-IP assays showed that PcTrim can interact with the virus protein VP26. PcTrim restricts the expression level of dynamin, which is involved in the regulation of phagocytosis, by inhibiting AP1 entry into the nucleus. AP1-RNAi effectively reduced the expression levels of dynamin and inhibited host cell endocytosis of WSSV in vivo. Our study demonstrated that PcTrim might reduce early WSSV infection by binding to VP26 and then inhibiting AP1 activation, resulting in reduced endocytosis of WSSV in crayfish hemocytes. Video Abstract.


Geographical variation mortality from ischaemic heart disease in England and Wales.
Analysis ofthe proportional mortality attributed to ischaemic heart disease, adjusted for age, reminds us that many of the well known geographical, environmental, social, and economic variations within England and Wales are not disease specific.


Progress and perspectives of enzymatic preparation of human milk fat substitutes.
Human milk fat substitutes (HMFS) with triacylglycerol profiles highly similar to those of human milk fat (HMF) play a crucial role in ensuring the supply in infant nutrition. The synthesis of HMFS as the source of lipids in infant formula has been drawing increasing interest in recent years, since the rate of breastfeeding is getting lower. Due to the mild reaction conditions and the exceptionally high selectivity of enzymes, lipase-mediated HMFS preparation is preferred over chemical catalysis especially for the production of lipids with desired nutritional and functional properties. In this article, recent researches regarding enzymatic production of HMFS are reviewed and specific attention is paid to different enzymatic synthetic route, such as one-step strategy, two-step catalysis and multi-step processes. The key factors influencing enzymatic preparation of HMFS including the specificities of lipase, acyl migration as well as solvent and water activity are presented. This review also highlights the challenges and opportunities for further development of HMFS through enzyme-mediated acylation reactions.


Regulation of inflammatory pathways by an a-tocopherol long-chain metabolite and a d-tocotrienol-related natural compound.
Vitamin E is the most important lipid antioxidant which is widely used to prevent age-associated diseases. In the liver a-tocopherol (a-TOH), the most active isomer, is metabolized by side-chain truncation. Hydroxylation and oxidation steps in peroxisomes form the long-chain metabolite (LCM) a-13'-COOH, which has been recently reported by our group to occur in human serum. Only little is known about the modes of action of the LCM. We therefore investigate the influence of the physiologically relevant a-13'-COOH and the tocotrienol (T3)-related garcinoic acid (GA) on LPS-induced inflammatory response of murine macrophages (mMF). We report here that a-13'-COOH occurs in human serum and can be detected by LC/MS-QTOF which provides evidence for its systemic bioavailability. Translating these results into mechanistic studies we use semi-synthetically derived LCM starting with garcinoic acid, isolated from the bitternut Garcinia kola, because LCMs are not commercially available as pure compounds. We also report that a-13'-COOH and GA inhibit pro-inflammatory pathways in comparison to a-TOH in LPS-stimulated mMF. A screening of inflammation-related genes showed significant decreases of Il1ß by all compounds, while Il6 and Tnfa were only down-regulated by GA. However Cox2 and iNos were significantly reduced on mRNA and protein level by more than 70% and also the formation of signaling molecules, such as NO and PGE2, was significantly reduced by a-13'-COOH and GA. Key role in regulation of inflammatory response is regulated by activation of NF?B along with p65 subunit translocation. Neither expression nor translocation were regulated by a-13'-COOH and GA. The LCM and d-T3 show high activity in inhibiting pro-inflammatory pathways and associated signal transduction. We speculate that physiological a-LCM represent a new class of regulatory metabolites.


Regulation of aphid populations by aphidiid wasps: does parasitoid foraging behaviour or hyperparasitism limit impact?
Aphidiid parasitoids (Hymenoptera: Aphidiidae) of aphids generally exploit only a small percentage of the available host resources in the field. This limited impact on aphid populations has often been explained as a consequence of hyperparasitism. We propose that a wasp's reproductive strategy, as opposed to hyperparasitism, is the dominant factor in aphidiid population dynamics. A wasp's foraging efficiency and oviposition decisions are influenced by several variables, including searching behaviour between and within patches, host choice (as modified by the aphids' defensive behaviours), and plant structural complexity. Two broadly different patterns of host exploitation have evolved in aphidiid wasps in relation to ant-aphid mutualism. Firstly, in species that are exposed to predation and hyperparasitism, a female may leave a patch before all suitable hosts are parasitized. Because predators and hyperparasitoids tend to aggregate at high aphid or aphidiid densities, or in response to aphid honeydew, this strategy enables females to reduce offspring mortality by "spreading the risk" over several host patches. Secondly, in species that have evolved mechanisms to avoid aggression by mutualistic ants, females are able to exploit a hyperparasitoid-free resource space. Such species may concentrate their eggs in only a few aphid colonies, which are thus heavily exploited. Although hyperparasitism of species in the first group tends to reach high levels, its overall impact on aphid-aphidiid population dynamics is probably limited by the low average fecundity of most hyperparasitoids. We discuss the foraging patterns of aphidiid wasps in relation to aphid population regulation in general, and to classical biological control in particular. We argue that a parasitoid's potential to regulate the host population is largely determined by its foraging strategy. In an exotic parasitoid, a behavioural syndrome that has evolved and presumably is adaptive in a more diverse (native) environment may, in a more uniform (managed) environment, result in suboptimal patch-leaving and oviposition decisions, and possibly increased resource usage.


Modulation of the conductance of a 2,2'-bipyridine-functionalized peptidic ion channel by Ni2+.
An alpha-helical amphipathic peptide with the sequence H2N-(LSSLLSL)3-CONH2 was obtained by solid phase synthesis and a 2,2'-bipyridine was coupled to its N-terminus, which allows complexation of Ni2+. Complexation of the 2,2'-bipyridine residues was proven by UV/Vis spectroscopy. The peptide helices were inserted into lipid bilayers (nano black lipid membranes, nano-BLMs) that suspend the pores of porous alumina substrates with a pore diameter of 60 nm by applying a potential difference. From single channel recordings, we were able to distinguish four distinct conductance states, which we attribute to an increasing number of peptide helices participating in the conducting helix bundle. Addition of Ni2+ in micromolar concentrations altered the conductance behaviour of the formed ion channels in nano-BLMs considerably. The first two conductance states appear much more prominent demonstrating that the complexation of bipyridine by Ni2+ results in a considerable confinement of the observed multiple conductance states. However, the conductance levels were independent of the presence of Ni2+. Moreover, from a detailed analysis of the open lifetimes of the channels, we conclude that the complexation of Ni2+ diminishes the frequency of channel events with larger open times.


The magnitude of chronic diabetes complications and its associated factors among diabetic patients attending the general hospitals in Tigray region, Northern Ethiopia.
Diabetes is a severe challenge to global public health since it is a leading cause of morbidity, mortality, and rising healthcare costs. 3.0 million Ethiopians, or 4.7% of the population, had diabetes in 2021. Studies on the chronic complications of diabetes in Ethiopia have not been conducted in lower-level healthcare facilities, so the findings from tertiary hospitals do not accurately reflect the issues with chronic diabetes in general hospitals. In addition, there is a lack of information and little research on the complications of chronic diabetes in Ethiopia. The objective of this study was to assess the degree of chronic diabetes complications and associated factors among diabetic patients presenting to general hospitals in the Tigray area in northern Ethiopia. As part of a multi-centre cross-sectional study, 1,158 type 2 diabetes (T2D) patients from 10 general hospitals in the Tigray region were randomly chosen. An interviewer-administered questionnaire, a record review, and an SPSS version 20 analysis were used to collect the data. All continuous data were presented as mean standard deviation (SD), while categorical data were identified by frequencies. Using a multivariable logistic regression model, the factors associated with chronic diabetes complications among T2D diabetic patients were found, and linked factors were declared at p 0.05. Fifty-four of people with diabetes have chronic problems. Hypertension (27%) eye illness, renal disease (19.1%), and hypertension (27%) eye disease were the most common long-term effects of diabetes. Patients with chronic diabetes complications were more likely to be older than 60, taking insulin and an OHGA (Oral Hyperglycemic Agent) (AOR = 3.00; 95% CI 1.73, 5.26), having diabetes for more than five years, taking more than four tablets per day (AOR = 1.63; 95% CI 1.23,2.15), and having high systolic and diastolic blood pressure. Patients with government employment (AOR = 0.48; 95% CI 0.26, 0.90), antiplatelet drug use (AOR = 0.29; 95% CI 0.16, 0.52), and medication for treating dyslipidemia (AOR = 0.54; 95% CI 0.35, 0.84), all had a decreased chance of developing a chronic diabetes problem. At least one chronic diabetic complication was present in more than half of the patients in this study. Chronic diabetes problems were related to patients' characteristics like age, occupation, diabetes treatment plan, anti-platelet, anti-dyslipidemia medicine, duration of diabetes, high Systolic BP, high Diastolic BP, and pill burden. To avoid complications from occurring, diabetes care professionals and stakeholders must collaborate to establish appropriate methods, especially for individuals who are more likely to experience diabetic complications.


Newborn birth weight correlates with placental zinc, umbilical insulin-like growth factor I, and leptin levels in preeclampsia.
The aim of the present study was to determine whether newborn birth weights were associated with insulin-like growth factor I (IGF-I), zinc, and leptin in preeclamptic and normotensive pregnancies. This study was done cross-sectionally and included 15 women with moderate preeclampsia (PE group) and 11 normotensive pregnant women (NT group) of similar gestational age. Maternal and umbilical cord serum levels of zinc, IGF-I, IGF binding proteins (IGFBPs), leptin, and placental zinc were assessed in each group. As compared with the NT group, the PE group had significantly (p <0.05) lower newborn birth weight [3.33 (3.11-3.55) vs. 2.80 (2.40-3.17) kg], maternal IGF-I [303 (276-364) vs. 198 (153-244) ng/mL], and umbilical IGF-I [87 (71-126) vs. 44 (26-98) ng/mL]. In addition, low IGFBP-3 and high IGFBP-1 were observed in the PE group. In the PE group, birth weight correlated positively with placental zinc (rho = 0.56, p = 0.04), maternal IGF-I (rho = 0.76, p = 0.004), umbilical cord IGF-I (rho = 0.75, p = 0.005), and umbilical cord leptin (rho = 0.61, p = 0.02) levels. Stepwise multiple regression analysis showed that among these variables, umbilical IGF-I was the major predictor of birth weight. In the NT group, birth weight did not correlate with any of these variables. The present study indicates that moderate preeclampsia is associated with low newborn birth weight, IGF-I, IGFBP-3, and high IGFBP-1 without significant changes in zinc and leptin levels. In addition, umbilical IGF-I was the major predictor of newborn birth weight.


Seasonal variations in the biophysical properties of rabbit aorta and its susceptibility to arteriosclerosis.
The physiological variations in the mechanical properties of rabbit aortae in relation to the periods of hair shedding were studied. The load-strain curves of the eight proximal thoracic segment in 15 shedding and 15 non-shedding male albino rabbits were analysed. The slope of the curves (tangent of the angle between the linear region of the load-strain curve and the strain axis) was decreased in the shedding animals compared to that of the non-shedding animals and the toe of the load-strain curves was significantly lower towards the x-axis in the shedding animals. The observations indicate a lower stiffness, that is increased elasticity, of the aortae of rabbits during hair shedding. The increased elasticity during hair shedding may explain the previously reported resistance to experimental arteriosclerosis caused by the hemodynamic strain elicited by exposure to systemic hypoxia. A decrease in the aortic content of collagen and of sulfated glycosaminoglycans, and an increase in the content of hyaluronic acid, may be of importance in the alterations of the mechanical properties of rabbit aorta during hair shedding.


Receptor type protein tyrosine phosphatase zeta-pleiotrophin signaling controls endocytic trafficking of DNER that regulates neuritogenesis.
Protein tyrosine phosphatase zeta (PTPzeta) is a receptor type protein tyrosine phosphatase that uses pleiotrophin as a ligand. Pleiotrophin inactivates the phosphatase activity of PTPzeta, resulting in the increase of tyrosine phosphorylation levels of its substrates. We studied the functional interaction between PTPzeta and DNER, a Notch-related transmembrane protein highly expressed in cerebellar Purkinje cells. PTPzeta and DNER displayed patchy colocalization in the dendrites of Purkinje cells, and immunoprecipitation experiments indicated that these proteins formed complexes. Several tyrosine residues in and adjacent to the tyrosine-based and the second C-terminal sorting motifs of DNER were phosphorylated and were dephosphorylated by PTPzeta, and phosphorylation of these tyrosine residues resulted in the accumulation of DNER on the plasma membrane. DNER mutants lacking sorting motifs accumulated on the plasma membrane of Purkinje cells and Neuro-2A cells and induced their process extension. While normal DNER was actively endocytosed and inhibited the retinoic-acid-induced neurite outgrowth of Neuro-2A cells, pleiotrophin stimulation increased the tyrosine phosphorylation level of DNER and suppressed the endocytosis of this protein, which led to the reversal of this inhibition, thus allowing neurite extension. These observations suggest that pleiotrophin-PTPzeta signaling controls subcellular localization of DNER and thereby regulates neuritogenesis.


A hybrid model for EEG-based gender recognition.
The gender recognition is an important research field to study evidence regarding some personal characteristics in the information and data society. However, some current traditional methods such as vision and sound have been exposed their own security weaknesses. Recently, biometric gender recognition based on Electroencephalography (EEG) signals has been widely used in information safety and medical fields. It is necessary to explore potential of using EEG to present a more robust and accurate result with larger training data based on sophisticated machine learning approaches. In this contribution, we present an automated gender recognition system by a hybrid model based on EEG data of resting state from twenty-eight subjects. These data are useful and handy to get insights into assessing the differences in personal gender. For achieving a good performance and a strong robustness, the system develops a hybrid model of combining random forest and logistic regression, and employs four common entropy measures to analyze the non-stationary EEG signals. Result also suggests that the recognition performance achieve an improved progress with an accuracy of 0.9982 and AUC of 0.9926 based on a nested tenfold cross-validation loop, implying that show a significant potential applicability of the proposed approach and is capable of recognizing personal gender.


Liver Resections for Colorectal Metastases in Patients Aged Over 75 Years.
Concerns regarding postoperative complications following liver resection for colorectal liver metastases (CLMs) in elderly patients may lead to preference for conservative therapy. The aim of this study was to evaluate the role of patient age in the development of postoperative complications. Surgical complications were evaluated in 712 patients who underwent surgery for CLMs over the past 13 years. Seventy-two patients (10.1%) were aged ≥75 years and 640 (89.9%) <75 years. The significance of the type of liver resection, preoperative American Society of Anesthesiologists classification (ASA), Child-Pugh classification,body mass index, quality of liver tissue and preoperative oncological treatment for the development of postoperative complications were evaluated. We did not find any difference in the incidence of early postoperative complications between the two groups of patients. A preoperative ASA score of 3.4 (p<0.001) was the principal factor for developing postoperative complications in patients aged ≥75 years. Postoperative complications in patients with an ASA score of 3.4 were more frequent when the body mass index was >26 kg/m2 (p<0.02). Patient age does not represent a contraindication to liver resection for CLMs. An ASA score of 3 or 4 and a body mass index >26 kg/m2 are risk factors for development of early postoperative complications.


Preparation of dopamine-modified sea squirt cellulose hydrogel dust-fixing agent to prevent raising of dust.
Sea squirts, a tunicate, are found in all oceans and can foul marine ports and aquaculture, mainly affecting shipping and biodiversity. In this study, cellulose was extracted from sea squirts, and its hydrophilic properties were improved by substituting the hydrogen ions of the cellulose -OH with dopamine. The modified cellulose was used to prepare a hydrogel for use as a dust-fixing agent (CDP) to reduce air pollution caused by dust. After response surface method optimization, the proportions of binder, water-retaining agent, wetting agent, and antifreeze in CDP were 0.97, 1.44, 0.23, and 6.32%, respectively. This composition improved the wetting ability and permeability of CDP on particle surfaces. CDP exhibited good water retention at -11-50 °C. CDP reduced the wind erosion rate of dust at a wind speed of 12 m/s to 1.18%. The molecular dynamics method was used to analyze the wetting process and mechanism of CDP, revealing that hydrogen bonds were the dominant force at the solid-liquid interface. The adsorption of CDP onto the surface of coal increased the number of hydrophilic points. Water molecules were adsorbed on these hydrophilic points through hydrogen bonding, improving the binding energy between the solid and liquid interfaces. The application of ascidian cellulose in dust control makes full use of the biological value of ascidians, promoting sustainable development of the global biological economy.


Consequences of larval intraspecific competition to stonefly growth and fecundity.
We conducted experiments in replicated circular streams to measure the effect of intraspecific larval density on growth rates, size at emergence, timing of emergence, and fecundity of two species of predatory stoneflies (Megarcys signata and Kogotus modestus, Perlodidae). Early instars of both species showed no significant effect of intraspecific larval density on mean growth rates, despite the observation that in the absence of competitors stoneflies ate on average, significantly more prey (Baetis bicaudatus, Ephemeroptera, Baetidae) than in the presence of competitors. However, larval size of stoneflies held at higher densities (two per chamber) diverged over time, resulting in a greater size variability (coefficient of variation) among Kogotus than in treatments with low densities of stoneflies (one per chamber). The effect of doubling the density of early-instar Megarcys larvae was also asymmetrical, resulting in one larger and one smaller individual. In contrast, doubling the density of last-instar stoneflies whose feeding rates declined significantly prior to emergence had few measurable consequences, except that male Megarcys, which continued to feed throughout the last instar, had lower average feeding rates in high-density than in low-density chambers, and emerged at a significantly smaller mean size. We conclude that competition between early-instar stonefly larvae results in an asymmetry of body sizes, but that competitive effects are reduced as larvae slow or cease feeding before emergence. Since larger females of both stonefly species produced more eggs, the probable cost to females of early-instar larval competition was a reduction in their potential contribution of offspring to the next generation. The cost of attaining a smaller body size for male stoneflies is unknown; but if, as in many other insects, larger males have greater reproductive success, larval competition may increase the opportunity for sexual selection among males. This hypothesis remains to be tested experimentally.


Development of three layered buccal compact containing metoprolol tartrate by statistical optimization technique.
The objective of this work to evaluate the effect of formulation variables on release properties and bioadhesive strength in development of three layered buccal compact containing highly water-soluble drug metoprolol tartrate (MT) by statistical optimization technique. Formulations were prepared based on rotatable central composite design with peripheral polymer ratio (carbopol 934P: HPMC 4KM) and core polymer ratio (HPMC 4KM: sodium alginate) as two independent formulation variables. The three layered buccal compact comprises a peripheral layer, core layer and backing layer. Four dependent (response) variables were considered: bioadhesion force, percentage MT release at 8 h, T50% (time taken to release 50% of drug) and release exponent (n). The release profile data was subjected to curve fitting analysis for describing the release mechanism of MT from three layered buccal compact. The main effects and interaction terms was quantitatively evaluated by quadratic model. The decrease in MT release was observed with an increase in both the formulation variables and as the carbopol: HPMC ratio increases the bioadhesive strength also increases. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of three layered buccal compact containing highly water-soluble drug MT.


Reduction of Fusarium proliferatum growth and fumonisin accumulation by ZnO nanoparticles both on a maize based medium and irradiated maize grains.
This study evaluated the antifungal effect of ZnO nanoparticles (ZnO-NPs) on Fusarium proliferatum growth and fumonisin accumulation both on a maize-based medium (in vitro) and on irradiated maize grains (in situ). The ZnO-NPs were obtained by drop-by-drop synthesis without further thermal treatment and characterized by scanning electronic microscopy/ energy dispersive X-ray spectroscopy (SEM/EDS) and X-ray diffraction (XRD). SEM analysis showed them as thin flakes of 200 × 200 nm, ~30 nm thickness and its purity were confirmed by XRD. During the in vitro assay ZnO-NPs (0, 0.8; 4, 8 g L-1) were evaluated at 25 °C during 21 days under darkness or photoperiod incubation (12/12 h light (cold white and black fluorescent lamps)/darkness) to determine its possible photocatalytic influence. Fumonisins were detected by high performance liquid chromatography coupled to mass spectrometry (HPLC- MS/MS). All ZnO-NPs concentrations significantly affected growth rates and FB1 accumulation by F. proliferatum RCFP 5033 (p < 0.05). Similar reduction of growth and FB1 (%) was observed at 0.8 and 8 g L-1 ZnO-NPs under photoperiod or darkness incubation. FB1 reduction was observed after 14 and 21 days, although the highest reduction occurred after 14 days under photoperiod incubation (84-98%). No clear light enhancing effect on the antifungal and anti-mycotoxin capability of the ZnO-NPs was observed. Morphological alterations in mycelia and conidia were observed by SEM. Under the in situ assay, the effect of the ZnO-NPs (0, 0.4, 0.8, 2 g kg-1) on growth rates and fumonisin B1, B2 and B3 accumulation by two F. proliferatum strains was evaluated on irradiated maize grains adjusted to 0.995, 0.98 and 0.97 aW in darkness at 25 °C during 21 days. Also, zinc acetate at 0.8 g kg-1 was included to compare their antifungal effect against the same ZnO-NPs concentration. Growth rates decreased significantly as ZnO-NPs concentrations increased. Higher than 60% of growth reduction was observed for both F. proliferatum strains. Zinc acetate significantly reduced growth, although it was less efficient that the same ZnO-NPs concentration. ZnO-NPs reduced total fumonisins accumulation by 71-99% at 0.8-2 g kg-1 ZnO-NPs and 0.98-0.995 aW. Moreover, 0.4 g kg-1 ZnO-NPs also produced significant reduction of the 3 fumonisins. This study showed the application of ZnO-NPs in maize grains could be a low cost and environmental impact strategy to control phytopathogen and toxigenic fungi such as F. proliferatum and to reduce fumonisins accumulation, both during crop development at preharvest stage and during maize storage.


A decision support system for quantitative measurement of operational efficiency in a blood collection facility.
A decision support system (DSS) is presented that allows users to input, analyze, and output data derived from blood banking operations. The DSS developed is a hybrid system that is both data and model driven. The system provides information, models, and data manipulation tools to assist users in the quantitative measurement of the operational efficiency in a blood collection facility. A relational database was developed to address the four major variables, which impact the cost per unit of blood being collected. Using visual basic, a user interface and mathematical model were developed establishing the relationships to analyze cost per unit of collected blood. Using inputs from users and historical financial data, the DSS calculates the cost per unit as each of the major variables is altered. Real life situations by the mobile operations team at a blood collection facility were used to test the DSS.


In Vitro Reconstitution of Human Mitochondrial Transcription.
In vitro assay based on a reconstituted mitochondrial transcription system serves as a method of choice to probe the functional importance of proteins and their structural motifs. Here we describe protocols for transcription assays designed to probe activity of the human mitochondrial RNA polymerase and the transcription initiation complex using RNA-DNA scaffold and synthetic promoter templates.


Erratum to: First hyperpolarizability of cyclooctatetraene modulated by alkali and alkaline earth metals.
The original version of this article unfortunately contained a mistake. Schemes I and II were missing. These important components are given below.


Location of the cleavage sites on the SV 40 DNA map produced by the restriction endonucleases Pst 1 and Bam 1.
Restriction endonucleases from Providencia stuartii (Pst 1) and Bacillus amyloliquefaciens H (Bam 1) cleave SV 40 DNA at two and one specific sites, respectively. Using EcoRI and Hind III endonuclease restriction sites as reference, the two Pst I sites were mapped at 0.050; 0.265 and the Bam I site was mapped at 0.170 of the genome length, clockwise, from the single EcoRI cleavage site.


The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth.
Mesenchymal stem cells (MSCs) have acquired great interests for their potential use in the clinical therapy of many diseases because of their functions including multiple lineage differentiation, low immunogenicity and immunosuppression. Many studies suggest that MSCs are strongly immunosuppressive in vitro and in vivo. MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells, dendritic cells and natural killer cells. In addition, several soluble factors have been reported to involved in the immunosuppressive effects by MSCs such as TGF-β, HGF, PGE2, IDO and iNOS. These results suggest that MSCs can be used in the therapy of immune disorder diseases, prevention of organ transplantation rejection and tissue injury. In recent study, we demonstrated that MSCs in tumor inflammatory microenvironment might be elicited of immunosuppressive function. Thus, the application of MSCs in cancer therapy might have negative effect by helping tumor cells escaping from the immune surveillance.


Totally thoracoscopic surgical resection of left ventricular benign tumor.
The study objective was to explore the feasibility and safety of totally endoscopic resection of a left ventricular tumor through small chest incisions without robotic assistance. Four patients with a left ventricular tumor (1 papillary fibroelastoma, 1 lipoma, and 2 myxomas) underwent surgery with peripheral cardiopulmonary bypass. The mean age of patients was 58 ± 15 years. There were 3 female patients and 1 male patient. Through 3-port incisions in the right chest, pericardiotomy, bicaval cannulation, cardiac arrest, and atriotomy, left ventricular tumor resection was performed under thoracoscopy. All patients had successful resections. The cardiopulmonary bypass and aortic crossclamp times were 110 ± 14 minutes and 58 ± 19 minutes, respectively. The length of stay in the intensive care unit was 38 ± 27 hours. There were no mortalities or complications in this cohort. Patients were discharged 7 days after the operation. Transthoracic echocardiography showed that the cardiac tumor was completely removed without any residue 3 months after surgery. Totally endoscopic left ventricular tumor resection without a robotically assisted surgical system is feasible and reproducible. This technique could minimize surgical trauma and achieves complete tumor resection.


Dental care during pregnancy based on the pregnancy risk assessment monitoring system in Utah.
Although receiving dental care is recommended for women during pregnancy, getting such care remains low. This study will identify the level of dental care received during pregnancy and factors associated with care for a group of pregnant women in Utah. Analyses were based on 2793 pregnant women completing the 2014-2015 Utah PRAMS survey. Descriptive and bivariate techniques were used. Approximately 91.2% knew it was important to care for their teeth and gums during pregnancy, yet only 58.8% had their teeth cleaned during pregnancy. Those who knew such care was important were 1.4 (95% CI 1.1-2.0) times more likely to have their teeth cleaned during pregnancy. Although 18.8% needed to see a dentist for a problem, only 74.5% of them received treatment for the problem during pregnancy. Approximately 76.0% had dental insurance during pregnancy. Those with dental insurance were 1.9 (95% CI 1.5-2.4) times more likely to have their teeth cleaned and 1.6 (95% CI 1.2-2.2) times more likely to go to a dentist for needed treatment during pregnancy. Approximately 51.4% had a dental/health care worker talk with them about how to care for their teeth and gums. These women were more likely to know it was important to care for their teeth and gums during pregnancy (97.4% vs 87.6%, p < 0.0001). For women who received care for a problem during pregnancy, 70.0% had a dental/health care worker talk with them about how to care for their teeth and gums. These women were more likely to know it was important to care for their teeth and gums during pregnancy (95.2% vs 82.8%, p < 0.0001). Women who had their teeth cleaned the year prior to pregnancy were more likely to have their teeth cleaned during pregnancy (78.5% vs 21.5%, p < 0.0001). A large proportion of women knowing of the importance of dental care during pregnancy did not receive care. Knowledge of its importance during pregnancy, having a dental/health care worker talk with them about how to care for their teeth and gums, and having dental insurance during pregnancy are positively associated with dental care during pregnancy.


On the environmental control of oocyte maturation in a plethodontid salamander.
The relationship between condition and oocyte maturation was experimentally studied in Plethodon cinereus. Gravid females with immature oocytes were collected in September and maintained on different feeding regimes for 180 days. An index of salamander condition was derived. There was no significant relationship between the number of maturing oocytes and condition of the salamander at the end of the experiment, but oocyte size was signifiantly related to condition. A significant regression relationship was found for oocyte number and initial body weight, suggesting that condition may affect oocyte number early in the reproductive cycle. The implications of environmental induction of oocyte number for affecting clutch size and fitness are discussed.


[Comparative studies on the stability of aqueous drug solutions in the isothermal and the non-isothermal short-time test as well as in the long-time test. Part 2: The stability of aqueous tetracaine solutions in the non-isothermal short-time test (author's transl)].
A study of the hydrolytic degradation of tetracaine solutions at various pH values demonstrates that the results from non-isothermal stability testing with logarithmic rise in temperature are in good agreement with the activation energies determined, under analogous conditions, by means of the isothermal short-time test and long-time test. The range of the maximum of stability is more clearly evinced by the non-isothermal short-time test than by the isothermal stability test. The comparison of the two methods reveals that the deviation of the reaction rate constants is greater in the non-isothermal test, which is due to the calculation required for the logarithmic rise in temperature. The results obtained with tetracaine evidence that the non-isothermal stability test is an appropriate method for the rapid determination of stability parameters (e.g. stability maximum, hydrolysis velocities) in the frame-work of testing potential drugs for stability and in the optimization of prescriptions.


Elimination of CD4(+)CD25(+) T cell accelerates the development of glomerulonephritis during the preactive phase in autoimmune-prone female NZB x NZW F mice.
The role of CD4(+)CD25+ T cell in glomerulonephritis (GN) development during the preactive phase was investigated in autoimmune-prone female NZB x NZW F1 (B/WF1) mice. The administration of anti-mouse CD25+ T-cell monoclonal antibody (PC61.5) 3 days after birth induced the development of GN with an increase in IgG2a antinuclear antibody, productions of IL-6 and IFN-gamma, whereas TGF-beta1 production decreased, compared to untreated control mice. The present study results suggest that CD4(+)CD25+ T cells may, at least in part, downregulate the development of GN during the preactive phase in B/WF1 mice.


Behavior Analysts to the Front! A 15-Step Tutorial on Public Speaking.
Mainstream prominence was Skinner's vision for behavior analysis. Unfortunately, it remains elusive, even as we approach the 110th anniversary of his birth. It can be achieved, however, and there are many routes. One that seems overlooked in many (most?) behavior analytic training programs is what I call the front of the room. The front of the room is a very powerful locus for influencing people. Mastering it can turn a commoner into a king; a middling man into a mayor; or a group of disorganized, dispirited people into an energized force marching into battle. The most powerful members of our species had their most memorable moments at the front of the room. If so much is available there, why is mastery of it in such short supply, not just in behavior analysts but in the population at large? In this paper, I address why, argue that the primary reason can be overcome, and supply 15 behaviorally based steps to take in pursuit of front of the room mastery.


Ultrastructure of immotile spermatozoa in an infertile male: a spectrum of structural defects.
A healthy well-androgenized male with no apparent defects of the endocrine system or ciliated epithelium presented with suspected infertility. A detailed electron-microscopic analysis of the semen showed viable but immotile spermatozoa manifesting a complex spectrum of fine-structural defects primarily in the flagella. The complex of deficits that can be appreciated only at the fine-structural level underscores the importance of electron-microscopic analysis in the evaluation of semen samples where the primary defect is a lack of motility.


Evidence of air pollution-related ocular signs and altered inflammatory cytokine profile of the ocular surface in Beijing.
We evaluated how different degrees of air pollution affect the ocular surface of a cohort of human subjects in Beijing by correlating in-patient test outcomes with tear cytokines. A cross-sectional study involving 221 volunteers was carried out in different districts of Beijing. Air pollution indices were recorded for 7 d (including the visit day). The indices recorded were the air quality index (AQI), which is a dimensionless measure that quantitatively describes the state of air quality, concentrations of particulate matter smaller than 2.5 μm (PM2.5) and 10 μm (PM10), sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2). The Ocular Symptom Disease Index (OSDI) questionnaire provided. Subsequently, subjects underwent slit-lamp examination, which included meibomian gland examination, conjunctival congestion score, conjunctivochalasis grade, tear meniscus height (TMH), tear breakup time (TBUT), corneal fluorescein staining (CFS), Schirmer I test, and conjunctival impression cytology. The concentrations of vascular endothelial growth factor (VEGF), interleukins (IL)-1β, IL-6 and IL-8 in tears were measured by microsphere-based immunoassay analysis. According to the value of the AQI, participants are divided into a slightly polluted (SP) group (n = 103) which the AQI value is less than or equal to 100 and a heavily polluted (HP) group (n = 118) whose AQI value is more than 100. Air pollution is related to ocular discomfort based on tear cytokine concentrations. PM2.5, PM10 and NO2 were positively correlated with OSDI, MG expressibility, meibum score, meiboscore, conjunctival congestion score, Schirmer I test value, TMH, goblet-cell density, concentrations of IL-6, and VEGF were negatively correlated with TBUT. PM2.5 and PM10 appear to be the major risk factors to the ocular surface, with NO2 being another important risk factor based on this study. The symptoms and signs of eye discomfort in the SP group were significantly less severe than those in the HP group, and tear cytokine concentrations (IL-6 and VEGF) were lower. Air pollution degrees were significantly correlated with tear cytokine concentrations, indicating an alteration of cytokine balance at the ocular surface under different degrees of air pollution.


Development of liposomes entrapped in alginate beads for the treatment of colorectal cancer.
Folic Acid conjugated liposomes encapsulating Oxaliplatin (L-OHP) were entrapped in alginate beads and further coated with Eudragit-S-100 for effective delivery to colon tumors. Liposomes were prepared by cast film method and folic acid was coupled on the surface of liposomes. They were further entrapped in alginate beads which were Eudragit coated for degradation in the colonic region. The prepared beads were characterized for shape and surface morphology, percentage entrapment efficiency and drug release studies. The in vitro drug release was investigated using a USP dissolution paddle type apparatus in different simulated gastrointestinal fluids. In vivo studies of the beads containing free drug, folic acid coupled and uncoupled liposomes bearing L-OHP was administered orally at the dose of 10mg L-OHP/kg body weight to tumor bearing NUDE/SCID mice. γ-Scintigraphic study showed that Eudragit coated alginate beads entered into the colon of Balb/c mice between 4.20 and 4.50h after oral administration. In vivo data showed that folic acid coupled liposomes entrapped in alginate beads delivered 2.82 ± 0.58 and 21.52 ± 2.76 μg L-OHP/g tissues in the colon and tumor after 12h, reflecting its targeting potential to colon and tumor. The results clearly demonstrate that Eudragit coated calcium alginate beads bearing folic acid coupled liposome can be used as a prospective carrier for drug delivery to colon specific tumor.


The results of denatured homologous vein grafts as conduits for secondary haemodialysis access surgery.
To determine the value of denatured homologous vein grafts as a conduit for secondary haemodialysis access. Retrospective clinical study. 2 University Hospitals. One-hundred-and-twenty-five patients received 195 grafts over a period of five years. Fifty-six first grafts (45%) functioned without complications throughout the study period of 5.8 years. Primary patency was 57% after 1 year and 25% after 3 years of follow-up. Of the initial grafts, 69 (55%) needed 161 interventions, for thrombosis (n = 59), stenosis (n = 43), failure beyond repair (n = 40), aneurysm (n = 12), infection (n = 4), steal syndrome (n = 1), and other causes (n = 2). Secondary patency was 76% at 1 year and 52% at 3 years of follow-up. A major advantage of these grafts was the low rate (2.6%) of infection. Aneurysm formation occurred 17 times in 195 grafts (8.7%). Denatured homologous vein graft is a good alternative in secondary access surgery.


Effect of phase ratio on van't Hoff analysis in reversed-phase liquid chromatography, and phase-ratio-independent estimation of transfer enthalpy.
In analysis of the thermodynamics of the transfer of a solute from the mobile phase to the stationary phase in reversed-phase liquid chromatography, it is nearly always assumed that the phase ratio is constant. This type of analysis is typically performed by applying a form of the van't Hoff equation, which relates the retention factor to temperature via the enthalpy and entropy of transfer. When non-linear van't Hoff plots are observed, it is often assumed that the enthalpy and entropy of transfer change with temperature. However, when the possibility of a change in the phase ratio is considered, it becomes apparent that non-linear van't Hoff behavior may or may not be due to changes in enthalpy or entropy. In this work, we present mathematical evidence that phase ratio changes, if they occur, can cause deviations from linearity in a van't Hoff plot. We also show that the phase ratio influence can be eliminated by considering the molecular difference between two solutes instead of the solutes themselves. The resulting selectivity van't Hoff plots may be linear, even when the van't Hoff plots of the two solutes are non-linear. In such cases, temperature-dependent phase ratio changes, and not necessarily changes in the transfer enthalpy, may be responsible for the curved van't Hoff plots of the individual solutes. In addition, we present chromatographic evidence that different solutes may "see" different thermodynamic phase ratios. It is clear that the concept of a phase ratio in reversed-phase chromatography is not nearly as well defined as a phase ratio in a bulk system like a liquid-liquid extraction.


Assessing the impact of a leadership and advocacy elective course in a college of pharmacy curriculum.
While the scope of a pharmacist's work has grown, continued advocacy is needed to ensure that their skillset is used to the best advantage of the patient. To accomplish this aim, the University of Utah College of Pharmacy created an elective advocacy and leadership class to train students in leadership and advocacy methods, with a focus on enabling students to practice advocacy within the state of Utah throughout the class. In addition to traditional lectures, this class asked students to apply the knowledge learned in class to projects within their sphere of influence. Activities included drafting their own bill, writing to a legislator, attending state legislative and board of pharmacy meetings, and a longitudinal quality improvement project. Students answered a pre- and post-class survey to assess their attitudes towards advocacy efforts and how those attitudes were affected by participation in the class. As expected, a positive change in attitude towards advocacy was observed, and students indicated that they were more likely to engage in advocacy activities in the future after participating in the course. Moreover, a real legislative outcome has been observed as the result of class projects. Enabling students to engage in advocacy activities and guiding them to effect real change is a valuable technique in pharmacy education. Similar efforts can be replicated in other institutions, and similar training should be expanded to required portions of the pharmacy curriculum.


In vivo comparison of two through-plane MR velocity mapping methods: fast Fourier encoding and phase mapping.
Magnetic resonance imaging maps of velocity were acquired with a 1.5-T system in 10 subjects in a plane perpendicular to the main pulmonary artery. Velocity images were successively acquired with a method developed from Fourier-encoding velocity imaging (FEVI) principles with eight gradient steps and one excitation, and with two-point phase-subtraction mapping. Reconstruction in FEVI was implemented by zero-filling interpolation around the eight gradient steps and then around the four central steps. The methods were compared by using estimates of noise in velocity measurements based on the difference between the experimental map and a smooth fitted map. For the same acquisition time, FEVI with four encoding steps was more precise in velocity measurements than phase mapping. Precision was further increased by the use of eight encoding steps, but acquisition time was doubled.


Clinical significance of CD166 and HER-2 in different types of gastric cancer.
Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.


Coordination Stoichiometry Effects on the Binding Hierarchy of Histamine and Imidazole-M2+ Complexes.
Histidine-M2+ coordination bonds are a recognized bond motif in biogenic materials with high hardness and extensibility, which has led to growing interest in their use in soft materials for mechanical function. However, the effect of different metal ions on the stability of the coordination complex remains poorly understood, complicating their implementation in metal-coordinated polymer materials. Herein, rheology experiments and density functional theory calculations are used to characterize the stability of coordination complexes and establish the binding hierarchy of histamine and imidazole with Ni2+ , Cu2+ , and Zn2+ . It is found that the binding hierarchy is driven by the specific affinity of the metal ions to different coordination states, which can be macroscopically tuned by changing the metal-to-ligand stoichiometry of the metal-coordinated network. These findings facilitate the rational selection of metal ions for optimizing the mechanical properties of metal-coordinated materials.


Selectivity of layered double hydroxides and their derivative mixed metal oxides as sorbents of hydrogen sulfide.
In the context of finding high efficient sorbent materials for removing hydrogen sulfide (H2S) from air stream, a screening study was performed to find the best combination of metals for the synthesis of layered double hydroxides (LDHs) and their derivative mixed metal oxides. Based on selectivity of 998 natural mineral species of sulfur-containing compounds, Cu(2+), Ni(2+) and Zn(2+) were selected as divalent metals, and Fe(3+), Al(3+) and Cr(3+) as trivalent metals to synthesis the LDHs sorbents. 10 LDHs materials and their calcined mixed metal oxides, Ni(0.66)Al(0.34), Cu(0.35)Ni(0.32)Al(0.33), Zn(0.66)Al(0.34), Cu(0.36)Zn(0.32)Al(0.32), Ni(0.64)Fe(0.36), Cu(0.35)Ni(0.31)Fe(0.34), Ni(0.66)Cr(0.34), Cu(0.35)Ni(0.31)Cr(0.34), Zn(0.66)Cr(0.34), Cu(0.33)Zn(0.32)Cr(0.35) were synthesized, characterized chemically and physically, and then tested using breakthrough test to determine their sulfur uptake. Ni(0.64)Fe(0.36) mixed metal oxides was found to have the best uptake of hydrogen sulfide (136 mg H₂S/g). Regeneration of spent Ni(0.64)Fe(0.36) mixed metal oxides was studied using two different mixture solutions, NaCl/NaOH and acetate-buffer/NaCl/NaOH. The latter mixture successfully desorbed the sulfur from the Ni0.64Fe0.36 sorbent for 2 cycles of regeneration/sorption.


[Gliding retirement, part-time work for the aged and partial pension problems and chances for an alternative form of terminating professional life].
The article deals with chances and risks of the concept "gliding retirement". Special notice is taken of partial-pension schemes. Possible consequences for employees with respect to their financial situation and to their working-conditions are discussed.


Alate production and sex ratio in colonies of the Neotropical termite Nasutitermes corniger (Isoptera; Termitidae).
1. Dissections of 49 entire Nasutitermes corniger (Motschulsky) colonies collected in Panama immediately prior to the nuptial flights give data on numbers, biomass and sex ratio of alates produced by individual colonies. 2) Twenty-six other colonies were collected and dissected in the early period of alate nymph development. Alate nymphs proceed through five instars, spending 5-8 months within the parental colony. 3) Even when comparing colonies of similar size, variation in reproductive output among N. corniger colonies in a population is marked. Mature colonies (neuter population size 50,000-400,000) generally produce 5,000-25,000 alates, although some large colonies had no fertile brood, at least during the year they were censused. 4) On average, colonies which produce alates have 35% of the colony biomass invested in alates (or late instar nymphs) shortly before the nuptial flight. 5) Female N. corniger alates are 1.2-1.4 times heavier (dry weight) than male nestmates. Numerical sex ratio among colonies is skewed toward males, while biomass "investment" sex ratio is not significantly different from 1:1. These data conform to Fisher's amended theory of expected sex ratio.


Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort.
Midostaurin added to intensive chemotherapy is the standard of care for acute myeloid leukemia (AML) with FLT3 mutations (FLT3mut). We analyzed the impact of midostaurin in 227 FLT3mut-AML patients included in the AML-12 prospective trial for fit patients ≤70 years (#NCT04687098). Patients were divided into an early (2012-2015) and late (2016-2020) cohorts. They were uniformly treated except for the addition of midostaurin in 71% of late group patients. No differences were observed in response rates or the number of allotransplants between groups. Outcome was improved in the late period: 2-year relapse incidence decreased from 42% vs 29% in early vs late group (p = 0.024) and 2-year overall survival (OS) improved from 47% vs 61% (p = 0.042), respectively. The effect of midostaurin was evident in NPM1mut patients (n = 151), with 2-yr OS of 72% (exposed) vs 50% (naive) patients (p = 0.011) and mitigated FLT3-ITD allelic ratio prognostic value: 2-yr OS with midostaurin was 85% and 58% in low and high ratio patients (p = 0.049) vs 67% and 39% in naive patients (p = 0.005). In the wild-type NPM1 subset (n = 75), we did not observe significant differences between both study periods. In conclusion, this study highlights the improved outcome of FLT3mut AML fit patients with the incorporation of midostaurin.


Age-related changes in lipid peroxidation products in rat adrenal gland.
Chloroform-methanol extracts from rat adrenals at five different ages (2, 6, 12, 18 and 24 months), were studied by fluorescence. After obtaining excitation and emission spectra, fluorescence intensity was measured at 365 nm excitation and 455 emission for all time points of aging. An additional study of lipid peroxidation employing a thiobarbituric acid reaction was made. Fluorescence intensity increased during aging from 16.39 × 10(3) arbitrary units of fluorescence per gram of tissue at 2 months, to 34.33 × 10(3) units at 24 months. Thiobarbituric acid reaction products expressed in nmol of malondialdehyde per gram of adrenal increased from 172.97 at 2 months to 640.83 at 24 months. One way analysis of variance revealed a statistically significant difference (p<0.05 and p<0.01 respectively). The results show an age-related steady increase in lipid peroxidation products in rat adrenals and suggest their accumulation in lipofuscin granules.


Hypertensive Urgency: An Emergency Department Pipeline to Primary Care Pilot Study.
Optimal triage of patients with hypertensive urgency (HU) in the emergency department (ED) is not well established. 2017 ACC/AHA hypertension (HTN) guidelines recommend treatment initiation and follow-up within 1 week. Objectives of our pilot study were to evaluate feasibility and impact of directly connecting ED patients with HU to outpatient HTN management on blood pressure (BP) control and ED utilization. ED patients with HU and no primary care physician were scheduled by a referral coordinator for an initial appointment in a HTN clinic embedded within a primary care practice. BP control and ED utilization over the subsequent 90 days were tracked and compared with BP at time of the referral ED visit, and ED utilization in the 90 days preceding referral. Data are reported for the first 40 referred patients. Average time to first visit was 7.8 days. Mean age was 51 years (range 28-76), 75% were African-American, and mean pooled 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 20.8%. Mean BP declined from 198/116 mm Hg at ED visit to 167/98 mm Hg at HTN clinic visit 1 to 136/83 by 6 weeks and was sustained at 90 days. Total ED visits for the group decreased from 61 in the 90 days prior to referral, to 18 in the 90 days after the first HTN clinic visit. In this pilot study, coordinated referral between the ED and primary care provides safe, timely care for this high ASCVD risk population and leads to sustained reductions in BP and ED utilization.


Current state of bladder diary: a survey and review of the literature.
The objectives of this study are (1) to assess practice patterns among urogynecology/female pelvic medicine and reconstructive surgery (FPMRS) providers regarding the use of bladder diaries (BD) and (2) to review the literature regarding BD. For the first objective, a survey was emailed to United States-based urogynecology providers in 2019 querying frequency of use of bladder diaries (FBD), indications, problems, patient education methods, and perception of utility. Chi-square tests and multiple logistic regression were performed. For the second objective, we reviewed literature published in English by searching the terms "voiding," "bladder," or "incontinence," in combination with "diary," "log," or "questionnaire." A total of 371 of 851 (43.5%) contacted providers responded. Nearly 80% were attending physicians, 75.5% of whom completed the FPMRS fellowship; 20.8% of all respondents and nearly 25% of fellowship-trained attendings reported FBD <20% in the last year. FPMRS providers were more likely to report FBD >80%. A total of 97.5% of respondents cited difficulty in using BD. Most (71.6%) taught patients to use BD themselves or shared responsibility with a nonphysician staff member (53.4%). BD is a validated and valuable instrument; however, there are obstacles to its use. Despite recent innovations including electronic and automated BD, there is a paucity of data regarding the provider-viewed challenges in implementing BD. The literature supports the use of BD; however, many survey respondents, including fellowship-trained attendings, never or rarely use BD. Most respondents reported difficulty in using BD. More research is needed to improve the ease, accuracy, and widespread adaptation of BD use in clinical practice.


Plasma and urine metabolic profiles are reflective of altered beta-oxidation in non-diabetic obese subjects and patients with type 2 diabetes mellitus.
The two primary pathophysiological characteristics of patients with type 2 diabetes mellitus (T2DM) are insulin resistance (IR) and beta cell dysfunction. It has been proposed that the development of IR is secondary to the accumulation of triacylglycerols and fatty acids in the muscle and liver, which is in turn thought to be secondary to an enzymatic defect in mitochondrial beta-oxidation. The purpose of the present study was to analyze the molecules of intermediary metabolism to determine if an alteration in mitochondrial function exists in T2DM patients and, if so, to determine whether this alteration is caused by excess nutrients or an enzymatic defect. Seventy-seven subjects were recruited and divided into four groups (21 T2DM patients, 17 non-diabetic overweight/obese subjects, 20 offspring of T2DM patients, and 19 healthy subjects). Anthropometric parameters were determined by air plethysmography, and biochemical and metabolic parameters were measured, including 31 acylcarnitines (ACs) and 13 amino acids quantified by MS/MS and 67 organic acids measured by GC/MS. Patients with T2DM showed elevation of short-chain ACs (C2, C4), a glycogenic amino acid (valine), a glycogenic and ketogenic amino acid (tyrosine), and a ketogenic amino acid (leucine) as well as altered excretion of dicarboxylic acids. T2DM offspring with abnormal glucose tolerance test GTT showed increased levels of C16. Subjects in the obese group who were dysglycemic also showed altered urinary excretion of dicarboxylic acids and lower levels of a long-chain AC (C14:2). These results suggest that mitochondrial beta-oxidation is altered in T2DM patients and that the alteration is most likely caused by nutrient overload through a different pathway from that observed in obese subjects.


Cytokines in antibacterial resistance: possible applications for immunomodulation.
Acquired resistance to intracellular bacteria is primarily mediated by T cells which--by secreting multiple interleukins (ILs)--activate antimicrobial activities in mononuclear phagocytes. Experimental infection of mice with Listeria monocytogenes and Mycobacterium bovis has helped to clarify the role of ILs in antimicrobial infection. These studies revealed: 1) application of IFN-gamma reduces the number of L. monocytogenes and treatment with anti-IFN-gamma antibodies worsens listeriosis; 2) in vitro, tuberculostatic and listericidal macrophage functions are activated by IFN-gamma, IL-4, and IL-6; 3) tumor necrosis factor (TNF) synergizes with IFN-gamma; 4) treatment with anti-TNF antibodies worsens listeriosis and interferes with M. bovis-induced granuloma formation; 5) concomitant application of mycobacterial products and TNF induces necrotic reactions. In humans at least some effects of IFN-gamma on macrophages may be mediated via 1,25-dihydroxyvitamin D3. These findings illustrate the multifaceted role of ILs in antimicrobial resistance and point to a central role of IFN-gamma.


Beta-caryophyllene mitigates the cognitive impairment caused by repeated exposure to aspartame in rats: Putative role of BDNF-TrKB signaling pathway and acetylcholinesterase activity.
Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. β-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.


Mapping of immune responses following wild-type and mutant ABeta42 plasmid or peptide vaccination in different mouse haplotypes and HLA Class II transgenic mice.
Although the recent clinical trial of the ABeta42 peptide vaccine against Alzheimer's Disease (AD) has been halted due to adverse events, the apparent clinical utility of this approach underscores the need to further improve the safety of the vaccine, as well as to understand the potential immunological basis for complications. In this study, we examine both humoral and cellular immune responses elicited by immunization with peptide or DNA encoding wild-type and the Flemish and Dutch mutations of ABeta42 (i.e. the beta amyloid peptide spanning amino acids 1-42) in mice of different immune haplotypes as well as HLA Class II transgenic mice. The Flemish and Dutch mutations have been associated with cerebrovascular hemorrhages in affected individuals. These data allow determination of potential immunological responses that could mediate pathology observed with mutant forms of amyloid beta, as well as lead to the generation of safer vaccine preparations. Following peptide or plasmid immunization, antibody responses were measured against the different ABeta42 peptides in an ELISA assay, while T cell epitopes were analyzed through interferon gamma ELISPOT and lymphocyte proliferation assays. B cell mapping studies indicated that sera from all of the haplotype mice vaccinated with any of the ABeta42 peptides reacted specifically to the first 10 amino acids of ABeta42 with the ABeta42 mutants eliciting higher immune responses. ELISPOT analysis, which accessed cellular immune responses indicated that mice expressed differences in Class I epitopes dependent on the different immune haplotypes. These results may have implications for the design of future ABeta42 based vaccines against Alzheimer's Disease.


Determination of Fructans in Infant Formula and Adult/Pediatric Nutritional Formula by Anion-Exchange Chromatography with Pulsed Amperometric Detection after Enzymatic Treatment: Collaborative Study, Final Action 2016.14.
Fructans are added to infant formula and adult nutritionals for their prebiotic effect. A method (AOAC 2016.14) was developed for their analysis which has already demonstrated excellent performance during single laboratory validation. To determine repeatability and reproducibility of the method through a collaborative study. Fourteen laboratories from 11 different countries enrolled for the study. Participants analyzed a practice sample, then 8 formula or adult nutritionals in blind duplicate. Results and any method modifications were reported to the study director. Twelve laboratories provided results on time for reporting. Precision results for five samples met the requirements of the Standard Method Performance Requirements (SMPR 2014.002), with RSDr ranging from 3.60 to 4.25% and RSDR ranging from 5.90 to 11.7%. The practice sample also met the requirements of SMPR 2014.002, with RSDr and RSDR of 2.53% and 6.70% respectively. Precision results for three test samples did not fully meet the SMPR, with RSDr ranging from 2.27 to 7.65% and RSDR ranging from 12.8 to 15.1%. After review, the AOAC Stakeholder Panel for Infant Formula and Adult Nutritional Expert Review Panel (SPIFAN ERP) concluded that the data presented mostly met the SMPR and hence recommended that the method to be advanced for adoption as an AOAC Final Action method. The method described in AOAC 2016.14 is suitable for the determination of fructans in infant formula and adult nutritionals.


Unilateral multicystic dysplastic kidney disease associated with ipsilateral ureteric bud remnant and contralateral duplex collecting system.
Congenital anomalies of the kidney and urinary tract are among the most common developmental malformations. The heterogeneity of these anomalies is very high, some of them are rarely discussed in the literature. Herein, we present a case of a 5-year-old male who was found to have a combination of unilateral multicystic dysplastic kidney associated with ipsilateral ureteric bud remnant and contralateral duplex collecting system.


Knowledge, attitudes, and practices toward added sugar consumption among female undergraduate students in Madinah, Saudi Arabia: A cross-sectional study.
This study aimed to evaluate knowledge, attitudes, and practices toward added sugar intake and the associations with nutrient intakes and weight status. This cross-sectional study was conducted among 190 healthy female undergraduate students at Taibah University, Madinah, Saudi Arabia. Demographic, knowledge and attitudes toward added sugar, dietary intake, and anthropometric data (i.e., height, weight, and waist circumference) were collected during face-to-face interviews. Approximately half of the students (n = 106; 55.8%) were aware of the health consequences of excessive intake of added sugar, but only 32.6% (n = 62) reported making an effort to reduce their added sugar intake. The data indicated that 8.42% of the students (n = 16) consumed carbonated soft drinks daily, 15.8% (n = 30) consumed fruit drinks daily, and 45.8% (n = 87) consumed sweets daily. Underweight students consumed higher quantities of added sugar (expressed as percent of total energy intake) compared with students in all other weight status groups. Results showed negative associations between percentage of added sugar intake and intakes of fiber, iron, zinc, vitamin D, body mass index, and waist circumference. Our findings indicated that a large proportion of young women had limited knowledge on the health consequences of excessive added sugar intakes. The observed inverse relationships between added sugar and micronutrient intakes and the weight status highlight the urgent need for expanded efforts to improve added sugar-related knowledge and promote the reduction of added sugar intake among young women.


Successful treatment with bortezomib in type-1 cryoglobulinemic vasculitis patient after rituximab failure: a case report and literature review.
Type-1 cryoglobulinemic vasculitis (CV) and mixed CV differ in their pathophysiology, clinical expression and treatment response. We report one patient with type-1 cryoglobulinemic vasculitis and skin ulcers that had remained active despite treatment with a variety of immunomodulating drugs including rituximab. The patient had a past medical history of non-Hodgkin lymphoma 10 years after CV onset for which she went into complete remission. The patient developed subsequent hematological anomalies in the serum and in the bone marrow without a definite diagnosis of myeloma. The patient finally went into clinical remission of her cryoglobulinemic vasculitis after treatment with bortezomib and dexamethasone. But she did not achieve an immunological remission and still had positive cryoglobulinemia and serum kappa-type free light chains. This suggests that bortezomib, a proteasome inhibitor that inhibits angiogenesis and production of paraproteins, is a promising treatment in type-1 cryoglobulinemic vasculitis.


TLR5 expression in the small intestine depends on the adaptors MyD88 and TRIF, but is independent of the enteric microbiota.
In our recent article Hörmann and coworkers have reported a role for epithelial cell-intrinsic TLR2 signaling for proliferation and renewal of the small intestinal epithelium. In this study, MyD88 and TRIF expression in the small intestine were affected by gut microbiota. Here, we report that in contrast to TLR2 and its co-receptor TLR1, TLR5 transcripts are not changed by presence of gut microbiota nor regulated through TLR2 or TLR4. Similar to TLR2 also TLR5 depends on MyD88 and TRIF adaptors. Our results indicate that TLR adaptor molecules could be determinants of TLR expression in the small intestine.