A mean-field model of the alkane-saturated lipid bilayer above its phase transition. I. Development of the model.
A statistical mechanical model of a bilayer of dipalmitoyl-3-sn-phosphatidylcholine molecules in equilibrium with an aqueous phase saturated with an n-alkane is presented. A mean-field approach developed in previous work on a solventless bilayer (Gruen, Biochim. Biophys. Acta. 595:161--183, 1980) is extended to allow alkane chains to exist in the hydrophobic core of the membrane. As the alkane chains are chemically similar to the lipid chains, much of the analysis follows directly from the solventless model. Novel features of the present model are the inclusion of (a) a term which models the free energy cost of creating space for alkane conformations, (b) a term which constrains the chains to pack evenly in the hydrophobic region of the membrane, and (c) a term which estimates the free energy of mixing of the lipid and alkane molecules in the plane of the bilayer. On uptake of alkane, the dimensions of the bilayer increase. Allowance is made for an increase in thickness and/or an increase in area per lipid. A thermodynamic framework is established which allows evaluation of the free energy of a bilayer of arbitrary dimensions with a view to predicting the equilibrium structure.


The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: significance for the use as anxiolytic/antidepressant drug.
Glutamatergic agents have been conceptualized as powerful, fast-acting alternatives to monoaminergic-based antidepressants. NMDA receptor antagonists such as ketamine or MK-801 are therapeutically effective, but their clinical use is hampered by psychotomimetic effects, accompanied by neurotoxicity in the retrosplenial and cingulate cortex. Antagonists of metabotropic mGlu5 receptors like MPEP elicit both robust antidepressant and anxiolytic effects; however, the underlying mechanisms are yet unknown. mGlu5 receptors closely interact with NMDA receptors, but whether MPEP induces neurotoxicity similar to NMDA receptor antagonists has not been elucidated. We show here using c-Fos brain mapping that MPEP administration results in a restricted activation of distinct stress-related brain areas, including the bed nucleus of stria terminalis (BNST), central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus (PVNH), in a pattern similar to that induced by classical antidepressants and anxiolytics. Unlike the NMDA antagonist MK-801, MPEP does not injure the adult retrosplenial cortex, in which it fails to induce heat shock protein 70 (Hsp70). Moreover, MPEP does not elicit to the same extent as MK-801 apoptosis in cortical areas at perinatal stages, as revealed by caspase 3 expression. These data identify new cellular targets for the anxiolytic and antidepressant effect of MPEP, indicating also in addition that in contrast to MK-801, it lacks the cortical neurotoxicity associated with psychotomimetic side-effects.


Step-wise enzymatic preparation and structural characterization of singly and doubly substituted arabinoxylo-oligosaccharides with non-reducing end terminal branches.
Shearzyme (GH10 endo-1,4-beta-D-xylanase) and two different alpha-L-arabinofuranosidases (AXH-m and AXH-d3) were used stepwise to manufacture arabinoxylo-oligosaccharides (AXOS) with alpha-L-Araf (1-->2)-monosubstituted beta-D-Xylp residues or alpha-L-Araf (1-->2)- and (1-->3) doubly substituted beta-D-Xylp residues from wheat arabinoxylan (AX) in a rather straightforward way. Four major AXOS (d-I, d-II, m-I and m-II) were formed in two separate hydrolyses. The AXOS were purified and the structures were confirmed using TLC, HPAEC-PAD, MALDI-TOF-MS and 1D and 2D NMR spectroscopy. The samples were identified as d-I: alpha-L-Araf-(1-->2)-[alpha-L-Araf-(1-->3)]-beta-D-Xylp-(1-->4)-beta-D-Xylp-(1-->4)-D-Xylp, d-II: alpha-L-Araf-(1-->2)-[alpha-L-Araf-(1-->3)]-beta-D-Xylp-(1-->4)-D-Xylp, m-I: alpha-L-Araf-(1-->2)-beta-D-Xylp-(1-->4)-beta-D-Xylp-(1-->4)-D-Xylp and m-II: alpha-L-Araf-(1-->2)-beta-D-Xylp-(1-->4)-D-Xylp. To our knowledge, this is the first report on structural (1)H and (13)C NMR analysis of xylobiose-derived AXOS d-II and m-II. The latter compound has not been reported previously. The doubly substituted AXOS were produced for the first time in good yields, as d-I and d-II corresponded to 11.8 and 5.6 wt% of AX, respectively. Singly alpha-L-Araf (1-->2)-substituted AXOS could also be prepared in similar yields by treating the doubly substituted AXOS further with AXH-d3.


Biology of the phylum nematomorpha.
Compared with most animal phyla, the Nematomorpha, also known as hair worms, is a relatively understudied metazoan phylum. Although nematomorphs make up only 1 of 3 animal phyla specializing solely on a parasitic life style, little attention has been focused on this enigmatic group scientifically. The phylum contains two main groups. The nectonematids are parasites of marine invertebrates such as hermit crabs. The gordiids are parasites of terrestrial arthropods, such as mantids, beetles, and crickets. Members of both of these groups are free-living as adults in marine and freshwaters respectively. In recent years, large strides have been made to understand this group more fully. New information has come from collection efforts, new approaches in organismal biology, modern techniques in microscopy and molecular biology. This review will focus on the advances made in four main areas of research: (1) morphology, (2) taxonomy and systematics, (3) life cycle and ecology and (4) host behavioural alterations. Recent research focus on the structure of both nectonematids and gordiids has added new insights on the morphology of adult worms and juveniles. The nervous system of gordiids is now well described, including the documentation of sensory cells. In addition, the availability of material from the juvenile of several species of gordiids has made it possible to document the development of the parasitic stage. New collections and reinvestigations of museum specimens have allowed for a critical reevaluation of the validity of established genera and species. However, traditional taxonomic work on this group continues to be hampered by two impeding factors: first is the lack of species-specific characters; and second is the problem of intraspecific variation, which has likely led to the description of numerous synonyms. Modern molecular techniques have been used recently to support independently the broad relationships among gordiids. During the turn of the millennium, the study of the life cycle and general ecology of gordiids enjoyed a revival. The pivotal outcome of this research was the domestication of a common American gordiid species, Paragordius varius. This species was the first of this phylum to be laboratory-reared. Through this research, the life cycle of several distantly related gordiid species was investigated. Other work showed that gordiids persist in the environment in the cyst stage by moving through different hosts by paratenesis. These cysts have been shown to retain infectivity for up to a year. These factors have likely contributed to the finding that gordiid cysts are one of the most common metazoans in some aquatic environments. Finally, recent work has focused on elucidating the mechanism of how gordiids make the transition from terrestrially based definitive hosts to a free-living aquatic environment. It has been shown that hosts are manipulated by the parasites to enter water. Using this study system, and using histology and proteomic tools, the method of manipulation used by these parasites is being further investigated. This manipulation, and the reaction of the cricket to this manipulation, has been postulated to benefit both the parasite and the host. Although large strides have been made within the last 10 years in the understanding of nematomorphs, we make the case that a lot of basic information remains to be uncovered. Although seemingly a daunting task, the recent advances in information and techniques lay a solid foundation for the future study of this unique group of parasites.


Sociodemographic inequality in exposure to COVID-19-induced economic hardship in the United Kingdom.
The COVID-19 pandemic led to a lockdown in European countries in the first half of 2020, including stay-at-home orders and closure of non-essential businesses. To mitigate the detrimental effects on the financial stress of employees and households, the UK government implemented a furlough scheme that temporarily secured earnings up to 80 percent of regular pay. Other employees were at risk of reduced work hours or permanent job loss. Using data from the UK Household Longitudinal Study COVID-19 Supplement, this study examines the extent to which different earnings groups and sociodemographic groups (gender, race/ethnicity, class background) became exposed to economic hardship between March and May of 2020. Results indicate that lower earnings groups were more than twice as likely to experience economic hardship relative to top quintile earners. Furthermore, among pre-COVID employed individuals, men and whites had a lower probability of being furloughed or dismissed from work. Analyses indicate that these are to a large extent attributable to gender earnings inequalities within occupations and the fact that women and racial-ethnic minorities are employed in essential occupations.


A critical review on environmental implications, recycling strategies, and ecological remediation for mine tailings.
Mine tailings, generated from the extraction, processing, and utilization of mineral resources, have resulted in serious acid mine drainage (AMD) pollution. Recently, scholars are paying more attention to two alternative strategies for resource recovery and ecological reclamation of mine tailings that help to improve the current tailing management, and meanwhile reduce the negative environmental outcomes. This review suggests that the principles of geochemical evolution may provide new perspective for the future in-depth studies regarding the pollution control and risk management. Recent advances in three recycling approaches of tailing resources, termed metal recovery, agricultural fertilizer, and building materials, are further described. These recycling strategies are significantly conducive to decrease the mine tailing stocks for problematic disposal. In this regard, the future recycling approaches should be industrially applicable and technically feasible to achieve the sustainable mining operation. Finally, the current state of tailing phytoremediation technologies is also discussed, while identification and selection of the ideal plants, which is perceived to be the excellent candidates of tailing reclamation, should be the focus of future studies. Based on the findings and perspectives of this review, the present study can act as an important reference for the academic participants involved in this promising field.


Arterial head vascularization cartographies of normal metencephalic dogs using magnetic resonance angiography.
The aim of our study was to establish head arterial cartographies-useful for the diagnosis of brain diseases leading to cerebral vascular modifications-by means of magnetic resonance angiography (MRA). Casts of the arterial vascular brain system were used to corroborate the MRA results as they can be easily rotated in nonvirtual three-dimensions and give an accurate view of the arteries calibre and origin. Two types of 3T MRA images were used: three-dimensional fast low-angle shot (3D-FLASH) acquisition sequenced every 20 s, paired with injection of a paramagnetic contrast medium, and three-dimensional time-of-flight (3D-TOF) acquisition sequenced every 300 s. 3D-FLASH acquisition gives very accurate images of the cerebral arteries and veins, but must be used with care in debilitated animals. 3D-TOF acquisition is less accurate and gives only images of the main cerebral arteries without showing the venous system. It is, however, a viable diagnostic method for monitoring vascular lesions (e.g., cerebral hemorrhages).


Neural correlates of intrusion of emotion words in a modified Stroop task.
Behavioural studies have demonstrated that the emotional Stroop task is a valuable tool for investigating emotion-attention interactions in a variety of healthy and clinical populations, showing that participants are typically more distracted by negative stimuli as compared to neutral or positive stimuli. The main aim of this study was to find and examine the neural correlates of this greater intrusion from negative emotional stimuli. Reliable reaction time (RT) and event-related potential (ERP) data were collected from 23 participants who performed a manual emotional Stroop task with short (40 ms) and long (500 ms) inter-trial intervals. In the short interval condition, participants were found to produce longer RTs for negative than neutral words, suggesting that these stimuli were more difficult to ignore. This RT effect disappeared in the long interval condition, although larger P1 amplitudes were found for the negative words. This suggests that differences in early attention allocation may be unrelated to the degree of intrusion at the behavioural level. In addition, a larger negative slow wave around 300-700 ms post-stimulus was observed in the long interval condition, but only for those negative words that produced prolonged RTs as compared to their matched controls. This late and broadly distributed effect is believed to reflect suppression of meaning representations.


Functional validation of Ca2+-binding residues from the crystal structure of the BK ion channel.
BK channels are dually regulated by voltage and Ca2+, providing a cellular mechanism to couple electrical and chemical signalling. Intracellular Ca2+ concentration is sensed by a large cytoplasmic region in the channel known as "gating ring", which is formed by four tandems of regulator of conductance for K+ (RCK1 and RCK2) domains. The recent crystal structure of the full-length BK channel from Aplysia californica has provided new information about the residues involved in Ca2+ coordination at the high-affinity binding sites located in the RCK1 and RCK2 domains, as well as their cooperativity. Some of these residues have not been previously studied in the human BK channel. In this work we have investigated, through site directed mutagenesis and electrophysiology, the effects of these residues on channel activation by voltage and Ca2+. Our results demonstrate that the side chains of two non-conserved residues proposed to coordinate Ca2+ in the A. californica structure (G523 and E591) have no apparent functional role in the human BK Ca2+ sensing mechanism. Consistent with the crystal structure, our data indicate that in the human channel the conserved residue R514 participates in Ca2+ coordination in the RCK1 binding site. Additionally, this study provides functional evidence indicating that R514 also interacts with residues E902 and Y904 connected to the Ca2+ binding site in RCK2. Interestingly, it has been proposed that this interaction may constitute a structural correlate underlying the cooperative interactions between the two high-affinity Ca2+ binding sites regulating the Ca2+ dependent gating of the BK channel. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain.


IGF-1 deficiency in combination with a low basic hBD-2 and hBD-3 gene expression might counteract malignant transformation in pleomorphic adenomas in vitro.
This study investigated the IGF-1-influence on oncological relevant genes in pleomorphic adenomas. Therefore A64-tumor cells were stimulated by recombinant IGF-1. After RNA-extraction, transcript levels of hBD-1, hBD-2, hBD-3, DEFA1/3, DEFA4, S100A4, Psoriasin, DOC-1, EGF, EGFR, and IGFR were analyzed by qRT-PCR at t = 0, 4, 8, 24, 48, and 72 hr. The gene-products were visualized by immunostaining. A64-tumor-cells were deficient for hBD-1 and IGF-1. IGF-1 downregulates hBD-2 and hBD-3 without influencing hBD-1-expression. IGF-1 only slightly affects DEFA1/3-, DEFA4-, S100A4-, Psoriasin-, DOC-1-, EGF-, EGFR-, and IGFR-gene-expression. IGF-1-deficiency combined with low basic hBD-2-gene-expression and hBD-3-gene-expression might counteract, whereas hBD-1-deficiency promotes malignant transformation in pleomorphic adenomas.


Mu insertion in feuD triggers the increase in nisin immunity in Lactococcus lactis subsp. lactis N8.
This study aims to explore how feuD mutation triggered the increase in nisin immunity of Lactococcus lactis L58, which was proven to be a feuD::Em-Mu mutant of Lc. lactis N8. The significant difference genes of Lc. lactis L58 and Lc. lactis N8 were compared at transcription and protein levels. Analysis revealed that the feuD mutation induced decrease in histidine-containing phosphocarrier protein PtsH (HPr) and increase in thioredoxin reductase TrxB (TR). Determination of iron concentration and cytoplasmic membrane potential (MP) showed the iron concentration decreased around 10% and the MP decreased approx. 14% in Lc. lactis L58. The increase in nisin immunity was dominated by TR up-expression by two main mechanisms in Lc. lactis L58. First, the TR-TRX (thioredoxin reductase) system changed the composition of cytoplasmic membrane by regulating the lipid metabolism to enhance the cells' resistance to nisin. Second, iron starvation stress induced decrease in MP; hence, the binding affinity of nisin to lipid II of Lc. lactis L58 decreased, which, in turn, increased the nisin immunity. The knowledge on regulation mechanism of nisin immunity was enriched, and the theoretical basis for improving nisin production in engineering strain could be provided.


Use of cultured permanent lines of intestinal epithelial cells for the assay of okadaic acid in mussel homogenates.
Two non-transformed intestinal epithelial cell lines (RIE-1 and IEC-6) and three intestinal carcinoma cell lines (HT-29, T84 and MCA-38) were used to detect the toxic effects due to okadaic acid in the presence of mussel tissue homogenates. Cytotoxicity was assessed by measurement of the metabolic conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide to its corresponding formazan dye. All of the cell lines were sensitive to okadaic acid, with HT-29, RIE-1 and IEC-6 showing the greatest response. Dilutions of whole mussel tissue homogenates caused some loss of viability in most of the cell lines but had no significant effect on the viability of RIE-1 cells. In no case did the mussel homogenate compromise the dose-response curve to okadaic acid when data were normalized to the appropriate control value. These intestinal epithelial cell lines may prove useful in the bioassay of okadaic acid and related toxins.


Cellular telephone transmission of 12-lead electrocardiograms from ambulance to hospital.
Currently, only single-lead, serial telemetry rhythm strips can be transmitted from ambulances. Triage of patients with chest pain and administration of thrombolytic therapy in ambulances is limited by the lack of specific electrocardiographic (ECG) diagnosis. A new technique is described using cellular telephone transmission of simultaneous 12-lead ECGs from ambulance to hospital to overcome this limitation. A portable 12-lead ECG installed in an ambulance was connected via modern link to a cellular telephone and digitized ECG information was transmitted to an ECG device in the hospital emergency room. Paramedics in the field placed adhesive patch electrodes and attached ECG wires. Field ECGs from 23 patients were compared with corresponding transmitted ECGs. There were no differences in heart rate, PR interval, QRS duration, QT interval or R- and T-wave axes. Baseline and transmitted ECGs had identical morphologic characteristics. Differences in R-wave amplitude in 5 transmitted tracings compared with hospital-recorded ECGs resulted in computer diagnosis of left ventricular hypertrophy by voltage, possibly due to differences in patient position. Twelve-lead ECGs can be easily transmitted from a moving ambulance using cellular telephones. This allows diagnosis before hospital arrival, improves prehospital triage of patients and may facilitate prehospital therapy with lidocaine or streptokinase. In addition, the cellular telephone link can convey both verbal and digitized information and thus improve on current telemetry systems.


Output congestion leads to compromised care in Peruvian public hospital neonatal units.
Peru is moving toward a universal health insurance system, and it is facing important challenges in the provision of public health services. As more citizens gain access to health insurance, the flow of patients exceeds the capacity of public hospitals to provide care with quality. In this study we explore the relationship between technical efficiency and patient safety events in neonatal care units of Peru's public hospitals. We use Data Envelope Analysis (DEA) with output congestion to assess the association between technical efficiency and patient safety events. We study 35 neonatal care units of public hospitals in Peru's Social Security Health System, and identify two undesirable (risk-adjusted) safety outcomes: neonatal mortality and near-miss neonatal mortality. We found that for about half of hospital's neonatal care units, technical efficiency is affected by output congestion. For those hospitals, patient safety is being compromised by receiving too many patients. Our results are consistent with public reports indicating that hospitals in the Peru's Social Security Health System are overcrowded, affecting efficiency and jeopardizing quality of care. We found that most congested hospitals are located in the capital city and suburban areas, and are more likely to be hospitals with the lowest and the highest level of care. Our results call for improvements in the patient referral system and capacity expansion.


Attractiveness and exploitation of decaying herbage by Drosophila in temperate woodland : An experimental analysis.
The Drosophila fauna of a deciduous flood plain forest rich in undergrowth near the river Isar, close to Munich, Germany, was surveyed in summer 1990. Decaying herbage baits (decay artificially induced) were set out to study the exploitation of that resource by Drosophila. Sixteen plant species belonging to several families dominant in the collecting area were tested. All attracted and produced drosophilid flies. Ten Drosophila species utilized decaying plant material as breeding sites; at least eight of the ten are polyphagous. Decaying stalks and leaves of Angelica sylvestris (Apiaceae) were examined in detail. In the case of the most frequent species of Drosophila attracted to A. sylvestris, the number of adults collected did not correlate with the number of flies emerging from the substrate. This was particularly true of D. limbata and D. phalerata. When oviposition and larval development of D. limbata and D. phalerata on A. sylvestris was tested in the laboratory, the number of offspring per female was the same in both species. The difference between these two species of the quinaria group in the exploitation of A. sylvestris in the field is therefore not due to differential suitability of the substrate.


A Cadaveric Study of the Buccal Fat Pad: Implications for Closure of Palatal Fistulae and Donor-Site Morbidity.
For the cleft surgeon, palatal fistulae after cleft palate repair remain a difficult problem, with a paucity of local tissue options to aid closure. Small clinical series have described the use of the buccal fat pad flap to repair palatal fistulae; however, there is no literature detailing the anatomical coverage of the flap. This study delineates the anatomy of the buccal fat pad flap to guide surgeons in patient selection and examines the residual buccal fat after flap harvest to provide new information with regard to possible effects on the donor site. Buccal fat pad flaps were raised in 30 hemicadavers. The reach of the flap across the midline, anteriorly and posteriorly, was recorded. In 18 hemicadavers, the entire buccal fat pad was then exposed to determine the effects of flap harvest on movement and volume of the residual fat. All buccal fat pad flaps provided coverage from the soft palate to the posterior third of the hard palate and all across the midline. Approximately three-fourths of flaps would cover the mid hard palate. The flap constitutes 36 percent of the total buccal fat pad on average, and a series of retaining ligaments were identified that may prevent overresection. The buccal fat pad flap is a useful tool for coverage of fistulae in the soft palate to the posterior third of the hard palate. In most cases, it will also reach the middle third; however, it is not suitable for more anterior defects. On average, two-thirds of the buccal fat pad remains within the cheek after flap harvest, which may protect against unwanted alteration in aesthetics.


Extraction of temporally correlated features from dynamic vision sensors with spike-timing-dependent plasticity.
A biologically inspired approach to learning temporally correlated patterns from a spiking silicon retina is presented. Spikes are generated from the retina in response to relative changes in illumination at the pixel level and transmitted to a feed-forward spiking neural network. Neurons become sensitive to patterns of pixels with correlated activation times, in a fully unsupervised scheme. This is achieved using a special form of Spike-Timing-Dependent Plasticity which depresses synapses that did not recently contribute to the post-synaptic spike activation, regardless of their activation time. Competitive learning is implemented with lateral inhibition. When tested with real-life data, the system is able to extract complex and overlapping temporally correlated features such as car trajectories on a freeway, after only 10 min of traffic learning. Complete trajectories can be learned with a 98% detection rate using a second layer, still with unsupervised learning, and the system may be used as a car counter. The proposed neural network is extremely robust to noise and it can tolerate a high degree of synaptic and neuronal variability with little impact on performance. Such results show that a simple biologically inspired unsupervised learning scheme is capable of generating selectivity to complex meaningful events on the basis of relatively little sensory experience.


[Development of the internal ear during the 1st trimester of pregnancy. Differentiation of the sensory cells and formation of the 1st synapses].
The inner ear of seventeen embryos, aged from 7 to 14 weeks after the fecondation, was investigated by optic and electron (transmission and scanning) microscopy. The timing of the first stages of the auditory and vestibular human receptor development is similar to the timing reported in animal studies, the vestibular epithelium development preceding by 2 to 3 weeks the cochlear development. The nerve fibers enter the sensory epithelia before the hair cell differentiation was histologically observed. At 9 weeks in the vestibular organs and 11 weeks in the cochlea, the hair cells are well differentiated and they exhibit typical synapses with nerve endings. Very early in the embryonic life, the auditory and vestibular receptors start their maturation and establish their connections with the peripheral and central nervous system; this indicates that the third month of pregnancy is a particularly sensitive period as far as the inner ear development is concerned.


Tracheo-esophageal anastomosis in treatment of chronic aspiration pneumonitis.
A patient underwent tracheo-esophageal anastomosis following repeated episodes of aspiration pneumonia after the resection of a meningioma at foramen magnum. The surgery eliminated the intractable problem with aspiration. This procedure is reversible, and restoration of the laryngeal function can be accomplished when the patient has recovered neurologically. If adequate neurologic recovery does not occur, the anastomosis can be left intact indefinitely.


Pharmacological activation of locomotor patterns in larval and adult frog spinal cords.
The effects of amino acids, catecholamines, and their agonists shown to elicit locomotor activity in several vertebrate species were examined in spinal animals and isolated nervous systems of developing tadpoles (Rana catesbiana) and adult frogs (R. catesbiana and pipiens). Elicited activity was correlated in spinal animals by video and electromyographic analysis, and in in vitro spinal cords by recordings of tail and hindlimb motor activity. Of the agents tested, only N-methyl-DL-aspartate (NMA), an amino acid agonist, was effective in eliciting motor activity in spinal animals. In isolated nervous systems, both NMA and D-glutamate added to the bath activated locomotor activity. NMA injected i.p. into tadpoles with high spinal cord transections elicited coordinated swimming motor activity in axial and hindlimb muscles that was roughly typical for the stage of development of the animal. In late stage tadpoles (st. XX), NMA also elicited wiping and alternating or synchronous (i.e. kicking or jumping) hindlimb movements. Addition of NMA or glutamate to a bath containing an in vitro tadpole spinal cord preparation elicited ventral root motor activity characteristic of swimming, but without a rostrocaudal phase lag. Rhythmic activity thought to underlie stepping and kicking was seen in lateral ventral rootlets innervating the hindlimbs. In adult frogs with high spinal cord transections, injection of NMA elicited a general sequence of spontaneous hindlimb motor functions: reflex wiping, stepping, and kicking or jumping. Isolated frog spinal cords were not responsive to bath applied NMA, under the present conditions. The activation by amino acids or their agonists of different motor functions in both larval and adult frogs, as well as in higher and lower vertebrates, suggests a general significance of amino acid-activated receptors in the neural networks controlling locomotor function.


Sequence analysis of porcine gut GLI-1.
A protein from porcine gut with 100 amino acid residues (porcine gut GLI-1) and having glucagon-like immunoreactivity has been characterized by partial sequences. The sequence of the C-terminal amino acid residues is -Met-Asn-Thr-Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala and includes the C-terminal amino acid residue sequence (-Met-Asn-Thr) of porcine glucagon. Evidence is presented that the glucagon sequence -Thr-Ser-Asp-Tyr-Ser-Lys-Tyr- is found in the gut GLI-1 as well. The data support the theory that gut GLI-1 contains the full glucagon sequence and that gut GLI-1 and glucagon are formed from a common precursor.


Cocaine-associated chest pain.
Current estimates establish that more than 30 million people in the United States use cocaine. Cardiovascular complaints commonly occur among patients who present to emergency departments(EDs) after cocaine use, with chest pain the most common complaint in several studies. Although myocardial ischemia and infarction account for only a small percentage of cocaine-associated chest-pain, physicians must understand the pathophysiology of cocaine and appropriate diagnostic and treatment strategies to best manage these patients and minimize adverse outcomes. This article reviews the pharmacology of cocaine, its role in the pathogenesis of chest pain with specific emphasis on inducing myocardial ischemia and infarction, and current diagnostic and management strategies for cocaine-associated chest pain encountered in the ED.


Effects of particle size distribution of potato starch granules on rheological properties of model dough underwent multiple freezing-thawing cycles.
In order to elucidate the mechanism underlying the effect of different-sizes potato starch on dough during freeze-thaw treatment, the rheological properties, moisture distribution, secondary structure, and relative crystallinity of dough were investigated. The results showed that the storage modulus (G'), loss modulus (G″), and complex modulus (|G*|) of dough increased as a result of the freeze-thaw treatment, and the effect was more obvious as the starch granular sizes increased. The higher β -sheet and T22 contents reflected the higher viscoelasticity and freeze-thaw sensitivity, which may be related to the higher degree expansion of amylose. In contrast, dough with small-sized starch had higher intermolecular interactions, and denser structure, lower water migration, showing that this has better resistance and higher stability. The presented mechanisms may contribute to the better understanding of the effects of freeze-thaw process on model dough properties.


A simple mathematical model for relapsing-remitting multiple sclerosis (RRMS).
Multiple sclerosis is one of the most common autoimmune-related neurological disorders affecting the central nervous system. One of its main properties is dissemination of lesions in time and space. Here, we propose a simple mathematical model to describe the stages of disease progression with recurrence. We tried to find the steady states and evaluated their stability to identify the necessary conditions to produce the recurrence. Also, we described the analytical results with some numerical simulations.


Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients.
Cord blood (CB) transplantation is an alternate source of human hematopoietic progenitor cells for allogeneic stem cell transplantation in children and adolescents with both malignant and nonmalignant diseases. Current limitations included delay in hematopoietic reconstitution, increased incidence of primary graft failure and slow cellular immunoreconstitution. These limitations lead to a significant increase in primary graft failure, infectious complications and increased transplant-related mortality. There is a number of experimental approaches currently under investigation including cellular engineering to circumvent these limitations. In this review, we summarize the recent findings of utilizing ex vivo CB expansion with Notch1 ligand Delta 1, mesenchymal progenitor cells, the use of human placenta-derived stem cells and CB-derived natural killer cells. Early and preliminary results suggest some of these experimental cellular strategies may in part ameliorate the incidence of primary graft failure, delays in hematopoietic reconstitution and/or slowness in cellular immune reconstitution following unrelated CB transplantation.


Intestinal mucosal triacylglycerol accumulation secondary to decreased lipid secretion in obese and high fat fed mice.
The ectopic deposition of fat in liver and muscle during obesity is well established, however surprisingly little is known about the intestine. We used the ob/ob mouse and C57BL6/J mice fed a high fat (HF) diet to examine the effects of obesity and the effects of HF feeding, respectively, on intestinal mucosal triacylglycerol (TG) accumulation. Male C57BL6/J (wild-type, WT) mice were fed low fat (LF; 10% kcal as fat) or HF (45%) diets, and ob/ob mice were fed the LF diet, for 3 weeks. In this time frame, the WT-HF mice did not become obese, enabling independent examination of effects of the HF diet and effects of obesity. Analysis of intestinal lipid extracts from fed and fasted animals demonstrated that the mucosa, like other tissues, accumulates excess lipid. In the fed state, mucosal triacylglycerol (TG) levels were threefold and fivefold higher in the WT-HF and ob/ob mice, respectively, relative to the WT-LF mice. In the fasted state, mucosa from ob/ob mice had threefold higher TG levels relative to WT-LF mucosa. q-PCR analysis of mucosal mRNA from fed state mice showed alterations in the expression of several genes related to both anabolic and catabolic lipid metabolism pathways in WT-HF and ob/ob mice relative to WT-LF controls. Fewer changes were found in mucosal samples from the fasted state animals. Remarkably, oral fat tolerance tests showed a striking reduction in the plasma appearance of an oral fat load in the ob/ob and WT-HF mice compared to WT-LF. Overall, the results demonstrate that the intestinal mucosa accumulates excess TG during obesity. Changes in the expression of lipid metabolic and transport genes, as well as reduced secretion of dietary lipid from the mucosal cells into the circulation, may contribute to the TG accumulation in intestinal mucosa during obesity. Moreover, even in the absence of frank obesity, HF feeding leads to a large decrease in the rate of intestinal lipid secretion.


Polymorphic transitions of diborane at sub- and near-megabar pressures.
Recent theoretical investigations of high-pressure structures of diborane have yielded many intriguing predictions which have so far remained untested due to challenges of acquiring experimental data at extreme pressures. Here we report new pressure-induced polymorphic transformations of crystalline diborane observed between 36 and 88 GPa by in situ Raman spectroscopy and interpreted using electronic structure calculations. Two previously unknown phase transitions are identified near 42 and 57 GPa, as evidenced by significant changes in the Raman profiles. The corresponding new phases, labeled IV and V, consist of B2H6 molecules and have triclinic unit cells (P), as deduced through evolutionary structure search and comparison of experimental and simulated Raman spectra. Density-functional calculations suggest that, at pressures above 110 GPa, phase V will form new molecular structures consisting of one-dimensional (BH3)n chains and will become metallic near 138 GPa. Our findings make a significant contribution to the elucidation of the structures and properties of diborane in the near-megabar pressure region.


High Fiber Cakes from Mediterranean Multipurpose Oilseeds as Protein Sources for Ruminants.
Fifteen oilseed cakes from sunflower, pomegranate, cardoon, tobacco and hemp were characterized with regard to chemical composition, Cornell Net Carbohydrate and Protein System (CNCPS) fractionation, in vitro digestibility of dry matter, neutral detergent fiber, and crude protein. All the cakes presented low moisture, rather variable ether extract contents and medium to high levels of crude protein and neutral detergent fiber. The cakes significantly differed in terms of CNCPS partitioning and in vitro digestibility. Tobacco and hemp cakes presented high contents of slow degradable fractions of crude protein and carbohydrate joined to good post-ruminal protein digestibility. Cardoon cakes presented the highest rumen protein degradability. Based on crude protein content and intestinal digestibility of rumen undegraded protein, cakes of tobacco and hemp showed the better potential as alternative protein supplements for ruminants, while pomegranate appears to be the least suitable for ruminant feeding.


Delayed multiligament PCL reconstruction is associated with a higher prevalence of intraarticular injury and may influence treatment.
The aim of this study was to investigate differences in concomitant injury patterns and their treatment in patients undergoing early (≤ 12 weeks) and delayed (> 12 weeks) primary multiligament posterior cruciate ligament (PCL) reconstruction (PCL-R). This study was a retrospective chart review of patients undergoing primary multiligament PCL-R at a single institution between 2008 and 2020. Multiligament PCL-R was defined as PCL-R and concurrent surgical treatment of one or more additional knee ligament(s). Exclusion criteria included isolated PCL-R, PCL repair, and missing data for any variable. Patients were dichotomized into early (≤ 12 weeks) and delayed (> 12 weeks) PCL-R groups based on the time elapsed between injury and surgery. Between-group comparison of variables were conducted with the Chi-square, Fisher's exact, and independent samples t-tests. A total of 148 patients were eligible for analysis, with 57 (38.5%) patients in the early and 91 (61.1%) patients in the delayed multiligament PCL-R groups. Concomitant LCL/PLC reconstruction (LCL-R/PLC-R) was performed in 55 (60%) of delayed multiligament PCL-Rs and 23 (40%) of early PCL-Rs (p = 0.02). Despite similar rates of meniscus injury, concomitant meniscus surgery was significantly more prevalent in the early (n = 25, 44%) versus delayed (n = 19, 21%) multiligament PCL-R group (p = 0.003), with a significantly greater proportion of medial meniscus surgeries performed in the early (n = 16, 28%) compared to delayed (n = 13, 14%) PCL-R group (p = 0.04). The prevalence of knee cartilage injury was significantly different between the early (n = 12, 24%) and delayed (n = 41, 46%) multiligament PCL-R groups (p = 0.01), with more frequent involvement of the lateral (n = 17, 19% vs. n = 3, 5%, respectively; p = 0.04) and medial (n = 31, 34% vs. n = 6, 11%, respectively; p = 0.005) femoral condyles in the delayed compared to the early PCL-R group. Given higher rates of chondral pathology and medial meniscus surgery seen in delayed multiligament PCL-R, early management of PCL-based multiligament knee injury is recommended to restore knee stability and potentially prevent the development of further intraarticular injury. Level III.


The romantic experiences of adolescents with a visible difference: exploring concerns, protective factors and support needs.
Injuries or conditions that affect appearance can increase adolescents' risk of psychosocial and interpersonal difficulties and may also impact on romantic relationships - an important aspect of adolescent development. A mixed method online approach explored the romantic experiences of 40 adolescents with a variety of visible differences. Young people identified appearance-related romantic concerns that cause distress, and impede the development and enjoyment of romantic relations. In contrast, some shared positive experiences and evidence of attitudes and behaviours that appear to protect against these concerns. Adolescents requested online peer support specific to their appearance-related needs. These findings can inform intervention development.


Making migraine easier to stomach: the role of the gut-brain-immune axis in headache disorders.
Headache disorders place a significant burden on the healthcare system, being the leading cause of disability in those under 50 years. Novel studies have interrogated the relationship between headache disorders and gastrointestinal dysfunction, suggesting a link between the gut-brain-immune (GBI) axis and headache pathogenesis. Although the exact mechanisms driving the complex relationship between the GBI axis and headache disorders remain unclear, there is a growing appreciation that a healthy and diverse microbiome is necessary for optimal brain health. A literature search was performed through multiple reputable databases in search of Q1 journals within the field of headache disorders and gut microbiome research and were critically and appropriately evaluated to investigate and explore the following; the role of the GBI axis in dietary triggers of headache disorders and the evidence indicating that diet can be used to alleviate headache severity and frequency. The relationship between the GBI axis and post-traumatic headache is then synthesized. Finally, the scarcity of literature regarding paediatric headache disorders and the role that the GBI axis plays in mediating the relationship between sex hormones and headache disorders are highlighted. There is potential for novel therapeutic targets for headache disorders if understanding of the GBI axis in their aetiology, pathogenesis and recovery is increased.


Clinical and oncological benefits of left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma.
This retrospective study aimed to clarify whether the postoperative prognosis differs between right and left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma. Preoperative images of 195 patients with perihilar cholangiocarcinoma were reexamined. Patients with Bismuth type I/II perihilar cholangiocarcinoma without a difference in extraductal tumor invasion between the right and left sides of the hepatic portal region were classified into those undergoing left (L group) or right (R group) hepatectomy. Twenty-three patients (11.8%) were classified into the L group and 33 (16.9%) into the R group. All eight patients with pTis/1 belonged to the L group. The L group had significantly less liver failure than the R group (p = 0.001). One patient (4.3%) in the L group and four patients (12.1%) in the R group died from postoperative complications. Among 48 patients with pT2, the L group tended to have better overall survival (median, 12.2 vs. 5.6 years; p = 0.072), but not recurrence-free survival (median, 9.1 vs. 3.6 years; p = 0.477), in comparison to the R group. Postoperative survival after left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma is expected to be as long as that after right hepatectomy.


Multiple Fragmentations: A Subnational Analysis of the Early Childhood Education and Care Workforce in Argentina.
The divided nature of the ECEC workforce is widely acknowledged. While scholarship has focused primarily on the consequences of the education-care divide, few studies have examined the workforce's fragmentation from a subnational perspective, particularly in the Global South. This article explores multiple fragmentations in the workforce, drawing on three provincial case studies in Argentina. The study included 17 interviews with national and subnational policy makers and three focus groups with ECEC workers. We explore ECEC workers' heterogeneous conditions and experiences across three provinces and demonstrate how vertical and horizontal fragmentation combine to create multiple fragmentations. We argue that subnational approaches are critical for better understanding the ECEC workforce's complexities and, ultimately, ECEC systems.


Plasminogen activator inhibitor-1 and tissue-type plasminogen activator are up-regulated during unilateral ureteral obstruction in adult rats.
The plasminogen activator (PA)-plasmin system has been shown to influence turnover of the extracellular matrix in various tissues. We examined the alteration of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in kidneys with unilateral ureteral obstruction in rats. Female rats that underwent ligation of the left ureter were sacrificed 12 hours, 1, 5 or 10 days later. The expressions of PAI-1 and t-PA was determined by reverse transcription-polymerase chain reaction and immunohistochemical studies in the obstructed and contralateral kidneys in each group. Control kidneys showed no PAI-1 messenger (m)RNA expression. After days 1 through 10 of unilateral ureteral obstruction the amount of PAI-1 mRNA significantly increased in obstructed compared with contralateral kidneys (p <0.01). Meanwhile, slight polymerase chain reaction products of t-PA were observed in control kidneys. After 12 hours through 10 days of unilateral ureteral obstruction, t-PA mRNA in obstructed and contralateral kidneys was significantly elevated compared with in control kidneys (p <0.05). No significant difference in t-PA was observed in the obstructed and contralateral kidneys in each group. Immunoreactivity to PAI-1 and t-PA was identified in obstructed kidneys. PAI-1 and t-PA are up-regulated in obstructed rat kidneys. Our results indicate that the PA-plasmin system has a role in the process of matrix accumulation and degradation during rat obstructive nephropathy.


Muscle fat contents rather than muscle mass determines nonalcoholic steatohepatitis and liver fibrosis in patients with severe obesity.
This study aimed to investigate the association of muscle fat contents, nonalcoholic steatohepatitis (NASH), and liver fibrosis in patients with severe obesity. Patients with severe obesity who underwent bariatric surgery were evaluated for NASH and liver fibrosis. Skeletal muscle was assessed by dual energy x-ray absorptiometry, and muscle fat contents (skeletal muscle fat index [SMFI]) were evaluated by computed tomography-based psoas muscle mass and density. A total of 104 patients with severe obesity were enrolled (57 with nonalcoholic fatty liver disease activity score <5 and 47 with NASH with nonalcoholic fatty liver disease activity score ≥5). SMFI was higher in patients with NASH than those without NASH (mean [SD], 39.0 [14.5] vs. 46.5 [14.2] for without NASH vs. with NASH; p = 0.009). SMFI was also correlated with hepatic steatosis grade, ballooning severity, and fibrosis stage. Multiple logistic regression analysis showed that SMFI was associated with higher risk of NASH and liver fibrosis (odds ratio = 2.37, 95% CI: 1.13-4.98, p = 0.022 for NASH; odds ratio = 2.93, 95% CI: 1.32-6.48, p = 0.008 for significant liver fibrosis). Muscle fat infiltration rather than muscle mass reflects the severities of hepatic steatosis and fibrosis in patients with severe obesity.


Experimental study of the effects of permafrost microorganisms on the morphofunctional activity of the immune system.
The immunobiological potential of a new microorganism species isolated from permafrost specimens (PMO strain 3M) collected from the Mammoth Mountain in Yakutia was studied in laboratory mice. PMO injected intraperitoneally in doses of 2500 to 50 × 10(6) microbial bodies caused characteristic dose-dependent effects on the structure and functions of the immune system (thymus and spleen indexes, functional activity of splenic macrophages, cellular and humoral immunity). Doses of PMO stimulating functional activities of both cellular and humoral immunity were detected.


Evaluation of the treatment options for COVID-19 patients using generalized hesitant fuzzy- multi criteria decision making techniques.
The breakout of the pandemic COVID-19 has affected numerous countries and territories worldwide. As COVID-19 specific medicines yet to be invented, at present the treatment is case specific, hence identification and evaluation of different prevalent treatment options based on various criteria and attributes are very important not only from the point of view of present pandemic but also for futuristic pandemic preparedness. The present study focuses on identifying, evaluation and ranking of treatment options using Multi Criteria Decision Making (MCDM). In this regard, the existing literature, doctors and scientist were interviewed to know the current treatment options in vogue and the scale of their importance with respect to the criteria. The criteria taken are side effect, regime cost, treatment duration, plasma stability, plasma turnover, time of suppression, ease of application, drug-drug interaction, compliance, fever, pneumonia, intensive care, organ failure, macrophage activation syndrome, hemophagocytic syndrome, pregnancy, kidney problem, age. This study extended Hesitant Fuzzy Set (HFS) to Generalized Hesitant Fuzzy Sets (GHFS). Generalized Hesitant Pentagonal Fuzzy Number (GHPFN) is developed. The properties of GHPFN are demonstrated. Two types of GHPFN has been described. The GHPFN (2nd type) along with MCDM tool Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) has been applied to rank the treatment options. The result of the study ranked 'Hydroxychloroquine' as the first alternative followed by, 'Plasma Exchange', 'Tocilizumab', 'Remdesivir' and 'Favipravir'. To check the robustness and steadiness of the proposed methodology, comparative analysis and sensitivity analysis has been conducted.


Biodegradation of polyurethanes by Serratia liquefaciens L135 and its polyurethanase: In silico and in vitro analyses.
Polyurethanes (PUs) are found in many everyday products and their disposal leads to environmental accumulation. Therefore, there is an urgent need to develop ecologically sustainable techniques to biodegrade and recycle this recalcitrant polymer and replace traditional methods that form harmful by-products. Serratia liquefaciens L135 secretes a polyurethanase with lipase activity, and this study explores the biodegradation of PUs by this bacterium and its enzyme through in silico and in vitro analyses. PUs monomers and tetramers were constructed in silico and tested with modeled and validated structure of the polyurethanase from S. liquefaciens. The molecular docking showed that all PUs monomers presented favorable interactions with polyurethanase (values of binding energy between -84.75 and -121.71 kcal mol-1), including PU poly[4,4'-methylenebis (phenyl isocyanate)-alt-1,4-butanediol/di (propylene glycol)/polycaprolactone] (PCLMDI). Due to repulsive steric interactions, tetramers showed less favorable interactions (values between 24.26 and -45.50 kcal mol-1). In vitro analyses evaluated the biodegradation of PUs: Impranil® and PCLMDI; this latter showed high binding energy with this polyurethanase in silico. The biodegradation of Impranil® by S. liquefaciens and its partially purified polyurethanase was confirmed in agar by forming a transparent halo. Impranil® disks inoculated with S. liquefaciens and incubated at 30 °C for six days showed rupture of the PU structure, possibly due to the formation of cracks visualized by scanning electron microscopy (SEM). PCLMDI films were also biodegraded by S. liquefaciens after 60 days of incubation, with the formation of pores and cracks visualized by SEM. The biodegradation may have occurred due to the action of polyurethanase produced by this bacterium. This work provides essential information on the potential of S. liquefaciens to biodegrade PUs through in silico analyses combined with in vitro analyses.


Non-tuberculous mycobacterial lung disease: diagnosis based on computed tomography of the chest.
To elucidate the accuracy and inter-observer agreement of non-tuberculous mycobacterial lung disease (NTM-LD) diagnosis based on chest CT findings. Two chest radiologists and two pulmonologists interpreted chest CTs of 66 patients with NTM-LD, 33 with pulmonary tuberculosis and 33 with non-cystic fibrosis bronchiectasis. These observers selected one of these diagnoses for each case without knowing any clinical information except age and sex. Sensitivity and specificity were calculated according to degree of observer confidence. Inter-observer agreement was assessed using Fleiss' κ values. Multiple logistic regression was performed to elucidate which radiological features led to the correct diagnosis. The sensitivity of NTM-LD diagnosis was 56.4 % (95 % CI 47.9-64.7) and specificity 80.3 % (73.1-86.0). The specificity of NTM-LD diagnosis increased with confidence: 44.4 % (20.5-71.3) for possible, 77.4 % (67.4-85.0) for probable, 95.2 % (87.2-98.2) for definite (P < 0.001) diagnoses. Inter-observer agreement for NTM-LD diagnosis was moderate (κ = 0.453). Tree-in-bud pattern (adjusted odds ratio [aOR] 6.24, P < 0.001), consolidation (aOR 1.92, P = 0.036) and atelectasis (aOR 3.73, P < 0.001) were associated with correct NTM-LD diagnoses, whereas presence of pleural effusion (aOR 0.05, P < 0.001) led to false diagnoses. NTM-LD diagnosis based on chest CT findings is specific but not sensitive. • Diagnosis of NTM-LD based on radiological findings showed high specificity. • Sensitivity of NTM-LD diagnosis was around 50 %. • Inter- observer agreement was moderate. • Identification of tree-in-bud pattern, consolidation and atelectasis led to correct diagnoses.


The effects of cannabidiol on behavioural and oxidative stress parameters induced by prolonged haloperidol administration.
We investigated the influence of oral cannabidiol (CBD) on vacuous chewing movements (VCM) and oxidative stress parameters induced by short- and long-term administration of haloperidol in a rat model of tardive dyskinesia (TD). Haloperidol was administered either sub-chronically via the intraperitoneal (IP) route or chronically via the intramuscular (IM) route to six experimental groups only or in combination with CBD. VCM and oxidative stress parameters were assessed at different time points after the last dose of medication. Oral CBD (5 mg/kg) attenuated the VCM produced by sub-chronic administration of haloperidol (5 mg/kg) but had minimal effects on the VCM produced by chronic administration of haloperidol (50 mg/kg). In both sub-chronic and chronic haloperidol groups, there were significant changes in brain antioxidant parameters compared with CBD only and the control groups. The sub-chronic haloperidol-only group had lower glutathione activity compared with sub-chronic haloperidol before CBD and the control groups; also, superoxide dismutase, catalase, and 2,2-diphenyl-1-picrylhydrazyl activities were increased in the sub-chronic (IP) haloperidol only group compared with the CBD only and control groups. Nitric oxide activity was increased in sub-chronic haloperidol-only group compared to the other groups; however, the chronic haloperidol group had increased malondialdehyde activity compared to the other groups. Our findings indicate that CBD ameliorated VCM in the sub-chronic haloperidol group before CBD, but marginally in the chronic haloperidol group before CBD. There was increased antioxidant activity in the sub-chronic group compared to the chronic group.


Capsaicin derived from endemic chili landraces combats Shigella pathogen: Insights on intracellular inhibition mechanism.
Ethnic tribals in northeast India have been growing and maintaining local chili landraces for ages. These chilies are known for their characteristic pungency and immense therapeutic properties. Capsaicin, a significant chili metabolite, is recognized as a natural drug for pain relief, diabetic neuropathy, psoriasis, arthritis, etc. In this study, we tried to observe the influence of locality factors on the pungency and bioactive features of Capsicum annuum L. landraces. We also checked the gastro-protective ability of these chilies, especially in the cure of shigellosis. Phytometabolite characterization and estimation were done through spectrophotometric methods. Preparative and analytical HPLC techniques were employed for extracting and purifying capsaicin-enriched fractions. Shigella flexneri growth retardation was determined through the broth dilution method. Gentamicin protection assay and ELISA were done to assess the intracellular invasion and IL-1β inflammasome production by S.flexneri. The correlation analyses postulated that phenols, flavonoids, chlorophylls, β-carotene, and capsaicin synthase upregulation strongly influenced capsaicin biosynthesis in chili cultivars. Correspondingly, the inhibitory efficacy of the HPLC-purified Balijuri-derived capsaicin was more effective than the Raja-derived capsaicin in inhibiting intracellular Shigella growth. Reduced levels of pro-inflammatory cytokine (IL1β) in capsaicin-treated Shigella-infected cells probably reduced inflammation-mediated intestinal damage, limiting bacterial spread. This investigation advocates the unique potential of local chilies in curing deadly 'shigellosis' with mechanistic evidence. Our observation justifies the traditional healing practices of the ethnic people of NE India.


Human leukocyte antigen DR status and clinical features in Japanese patients with type 1 autoimmune hepatitis.
Human leukocyte antigen (HLA) DR status affects the clinical features of autoimmune hepatitis. In Caucasians, patients with DR3 have poorer outcomes. In Japan, the relationship between HLA DR status and clinical features has yet to be fully examined. We investigated 79 patients with type 1 autoimmune hepatitis who underwent liver biopsy and were screened for HLA DR status by the polymerase chain reaction sequence specific oligonucleotide hybridization method. Fifty-five patients had DR4 and 23 had DR2. Thirteen patients had both DR2 and DR4. None had DR3. Of patients aged <30 years, 70% did not have DR4. A tendency toward higher serum levels of immunoglobulin G was seen in patients with DR4 compared to those without, while patients with neither DR2 nor DR4 had lower serum levels of immunoglobulin G than those with only DR2 and those with only DR4. Patients with DR2 had a lower frequency of concurrentautoimmune disease. Concurrence of thyroid disease was seen only in patients with DR4. The cumulative incidental rate of the normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was not associated with HLA DR status. HLA DR status is considered to affect the clinical features of Japanese patients with type 1 autoimmune hepatitis. Japanese patients with DR2 may have different clinical features from others. In addition, diagnoses of type 1 autoimmune hepatitis should be made carefully in Japanese patients with neither DR2 nor DR4 and in those aged <30 years.


[Traumatic arterial spasm. Reflections on several personal cases].
Four personal cases and the treatment adopted are described. The incidence of this event is discussed. Attention is drawn to what is felt to be the most suitable treatment of traumatic ischaemia with a possibility of underlying spasm at in the light of the existing knowledge.


Distinct chromosomal imbalances in pleomorphic and in high-grade dedifferentiated liposarcomas.
Using comparative genomic hybridization, DNA copy number changes were studied in 14 pleomorphic liposarcomas and compared to those detected in high-grade areas of 9 dedifferentiated liposarcomas. A total of 251 gains and 84 losses were detected. The most frequent gains involved subregions of chromosomal arms 12q and 20q (70% each), 5p (57%), 6q and 9q (52% each), 1q, 7p and 17p (48% each), 1p (43%), 6p and 17q (39% each), 20p and 22q (35% each) as well as 7q and 12p (30% each). The same subregions were also affected by 30 high level amplifications. The most frequent losses were found in subregions of chromosomal arms 13q (35%) as well as 11q and 12p (30% each). Overall, gains of chromosomal material were more frequent than losses (p < 0.001). There were significant differences in the frequency and distribution of recurrent chromosomal imbalances between pleomorphic liposarcomas and the dedifferentiated areas of dedifferentiated liposarcomas. Gains of chromosomal material detected predominantly in pleomorphic liposarcomas involved subbands 5p13-p15 (p < 0.010), 1p21 (p < 0.019), 1q21-q22 (p < 0.040) and 7q22 (p < 0.049). Conversely, high level amplifications within chromosomal subregion 12q13-q21 were only found in the dedifferentiated components of dedifferentiated liposarcomas (p < 0.001). Overall, both gains and the less pronounced losses of chromosomal material were more frequent in pleomorphic than in dedifferentiated liposarcomas (p < 0.001 and p < 0.025, respectively). These results show that pleomorphic liposarcomas display a considerable number of recurrent chromosomal imbalances that are essentially different from those present in high-grade areas of dedifferentiated liposarcomas. Therefore, genetic data are considered as a helpful diagnostic adjunct for the discrimination between these 2 types of liposarcoma. The overall higher frequency of chromosomal imbalances in pleomorphic as compared to dedifferentiated liposarcomas could account for the more aggressive biological behavior of pleomorphic relative to dedifferentiated liposarcoma types.


Comprehensive management of cardiometabolic risk factors.
Comprehensive management of cardiometabolic risk requires management of a patient's underlying risk factors. The initial approach to treatment demands a careful assessment of patient risk, using formal risk assessment tools (eg, the Framingham Risk Score and the National Cholesterol Education Program Adult Treatment Panel III definition of metabolic syndrome), combined with comprehensive knowledge of the patient. There is increasing evidence that lifestyle modification and pharmacotherapy can delay or prevent the progression of insulin resistance to diabetes and cardiovascular disease. Periodic reassessment of a patient's risk can assist in guiding long-term therapy to achieve optimal cardiometabolic health.


Antigen-induced T-cell changes: modulation by pharmacologic agents.
To determine the effect of pharmacologic modulation of alterations of peripheral blood T-cell subsets caused by antigen-induced bronchoconstriction, we administered albuterol immediately after antigen-induced bronchoconstriction in a double-blind to protocol to 12 atopic asthmatic subjects. We also administered cromolyn sodium before antigen to 7 of the same subjects. Peripheral blood T-cell subset composition (CD4, CD8, Ia) of a highly purified T-cell preparation was determined before, 24, 48, 72, and 168 h after bronchoconstriction. We found that placebo inhalation immediately after antigen-induced bronchoconstriction did not affect subsequent peripheral blood T-cell subset changes (decrease in CD4+ and increase in Ia+ T lymphocytes). In contrast, inhaled albuterol abolished these T-cell subset changes. Although cromolyn sodium significantly decreased the severity of antigen-induced bronchoconstriction, it did not affect T-cell subset composition changes at the dosage used. We conclude that albuterol can ablate T-cell subset changes associated with antigen-induced bronchoconstriction. Cromolyn sodium ameliorates bronchoconstriction, but has no affect on T-cell subset composition changes. This implies that T-cell changes and bronchoconstriction caused by antigen inhalation are mediated through different pathways.


Sclerosteosis in children.
Craniotubular dysplasias and craniotubular hyperostoses are a group of confusing disorders in which the cranial involvement may cause compression of facial and auditory nerves. Two of the hyperostotic conditions that regularly produce cranial nerve compression are sclerosteosis and the recessive form of endosteal hyperostosis (van Buchem's disease). Both have identical radiological features with cranial involvement presenting in childhood. The Dutch and South African cases have come from relatively close-knit communities, those in the latter country being Afrikaners who had their origins in Holland. The radiological features of three such cases of sclerosteosis are briefly presented.


Surviving versus thriving: The wellbeing of primary school aged children in Tonga.
To enable improvements in global child health, the focus must move beyond child survival to child wellbeing. In the Pacific Islands, the wellbeing of children has received little attention. This study aimed to investigate the wellbeing of children from three primary schools in Tonga. A cross-sectional survey was completed in three primary schools in Nuku'alofa with children aged 5-15 years. The study participants (256 children, 143 caregivers) completed the Child Health and Illness Profile - Child Edition, CHIP-CE (Version 1.0). On average, >70% of children and caregivers described home and school environments as positive. From the children's reports, boys had significantly lower scores for risk avoidance than girls (3.40 vs. 3.73, P < 0.001). Children aged 5-7 versus 8-15 years had significantly lower scores for satisfaction (3.63 vs. 3.92, P = 0.002), resilience (3.34 vs. 3.56, P = 0.016) and achievement (3.25 vs. 3.62, P = 0.002). From the caregivers' report, girls had significantly lower scores for academic performance than boys (3.60 vs. 3.81, P = 0.04). Boys had significantly lower scores for individual risk association compared to girls (3.93 vs. 4.29, P = 0.01). Overall CHIP-CE scores were lower than those of comparable populations in the West, while at the same time protective factors were documented. Understanding child wellbeing in the Pacific is critical for strengthening protective factors known to mitigate poor child health outcomes. Continuing to base global child health success on child survival alone misses opportunities for improving the wellbeing of nations.


Effect of Lagoon and Sea Water Depth on Gracilaria gracilis Growth and Biochemical Composition in the Northeast of Tunisia.
This study evaluated the growth and biochemical composition of farming Gracilaria gracilis (Stackhouse) M. Steentoft, L. M. Irvine & W. F. Farnham in the Bizerte Lagoon (BL) and Bizerte Bay (BB) in the North Coast of Tunisia, using lantern nets. Effects of site and depth on alga daily growth rate (DGR) and biochemical composition were investigated. The DGR was affected by culture site (1.42 ± 0.65% day-1 and 1.19 ± 0.34% day-1 for the BL and the BB respectively). Agar yield, was higher (p < 0.05) in the BB than the BL (23.31 ± 2.64% vs. 19.19 ± 2.32%) with a higher (p < 0.05) 3,6-anhydrogalactose (3,6-AG) contents (41.37 ± 3.68% vs 23.30 ± 5.40%) and a lower (p < 0.05) sulphate degree (6 ± 2.00% vs 8.80 ± 0.86%). The proteins contents were independent of the site and depth of culture (20.74 ± 7.22% and 22.02 ± 6.34% for the BL and the BB respectively). R-phycoerythrin (R-PE) contents were significantly higher (p < 0.05) in the BB (0.86 ± 0.31 mg g-1) than those obtained in the BL (0.33 ± 0.12 mg g-1). The salinity, transparency, nitrate and ammonium were monitored in both sites, and their influences were discussed. Our results suggest that G. gracilis cultured in Bizerte Bay can be used in a cascading biorefinery approach.


Tau in Alzheimer's disease.
Neurofibrillar protein aggregates containing tau are one of the major hallmarks of Alzheimer's disease (AD). In normal cells, tau stabilizes axonal microtubules, which are the tracks for intracellular traffic. In AD, tau becomes abnormally phosphorylated, aggregates into paired helical filaments and loses its ability to maintain the microtubule tracks. There is renewed interest in tau as a causative factor in neurodegenerative disease based on recently discovered mutations in the gene encoding tau. This article discusses how changes in tau protein could lead to retraction of neuronal processes and thus cell death and argues that tau pathology, rather than beta-amyloid, might be the most reliable indicative factor for AD.


Dysregulated thyroid hormones correlate with anxiety and depression risk in patients with autoimmune disease.
Autoimmune disease (AID) patients always present with increased risk of psychiatric disorders, and thyroid function or thyroid hormone may play a critical role in the development of anxiety and depression. Thus, this study aimed to assess the free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH) levels, and their correlations with anxiety/depression in patients with AID. Ninety-eight AID patients and 100 health controls (HCs) were recruited. Serum samples were obtained from all the participants to detect FT3, FT4, and TSH levels. Anxiety and depression were determined using the HADS assessment. HADS-Anxiety score, anxiety subject percentage, HADS-Depression score, and depression subject proportion were elevated in AID patients compared with HCs. FT3 and FT4 were downregulated while TSH was upregulated in AID patients compared with HCs. In AID patients, FT3 and FT4 negatively correlated with HADS-Anxiety score, and they were downregulated in patients with anxiety compared to patients without anxiety. Meanwhile, FT3 and FT4 were negatively associated while TSH level positively associated with HADS-Depression score. Besides, FT3 and FT4 reduced, but TSH level was of no difference in patients with depression compared to patients without depression. Additionally, increased FT4 independently correlated with both reduced anxiety risk and depression risk. FT3, FT4, and TSH are dysregulated, and FT4 has the potential to serve as an independent biomarker related to anxiety as well as depression in AID patients. These findings may provide some information on the values of thyroid hormones in facilitating the management of AID patients with anxiety/depression.


Selective sentinel lymphadenectomy: progress to date and prospects for the future.
The sentinel node (SN) concept was clearly outlined by Virchow in the mid-nineteenth century, and Braithwaite used the term "glands sentinel" in 1923. However, it was not until Morton, Cochran et al. published their landmark report in 1992 that the clinical relevance of the SN was fully appreciated. Since then, the validity of the concept has been confirmed in studies undertaken at a number of centers worldwide. It has become clear that SN status accurately reflects the status of the entire regional node field, not only in patients with melanoma but also in those with breast cancer and a wide range of other primary malignancies. New insights into lymphatic anatomy have been gained by preoperative lymphoscintigraphy, and the original blue dye mapping technique for SN identification has been supplemented by intraoperative use of a hand-held gamma probe to identify radioactivity in colloid particles injected at the primary tumor site. It has become clear that all three methods are required to achieve optimal accuracy of SN identification. Although SN assessment provides very important prognostic information, the results of randomized trials must be awaited to determine whether selective sentinel lymphadenectomy, with full regional node dissection if a positive SN is found, is of any therapeutic value. It is possible that SN positivity is merely a marker of disease that has the potential for hematogenous dissemination and systemic metastasis. As follow-up times extend, reported false-negative SN rates are increasing, and ways to reduce these false-negative rates are therefore being actively sought. Attempts are being made to increase the accuracy of SN identification, and to confirm true SN identity both at the time of surgery and retrospectively. The ultimate objective is to develop minimally invasive and even non-invasive methods of SN assessment, Proton magnetic resonance spectroscopy is one technique that might make it possible to achieve this goal, and avoid the present morbidity and cost of operative SN removal.


Safety and Effectiveness of Suture-mediated Arterial Closure Device in Hepatocellular Carcinoma Patients Who Underwent Drug-Eluting Beads Transarterial Chemoembolization.
The number of transarterial percutaneous procedures has risen over the years, consequently reducing puncture site related complications has become a necessity. To this end, the use of arterial closure devices has been growing progressively and their benefits have become a focus of research. The purpose of this study is to assess the safety and effectiveness of a suture-mediated closure device, Perclose ProGlide® (Abbott Vascular, Redwood City, CA), in patients with liver disease and hepatocellular carcinoma who underwent transarterial liver chemoembolization with drug-eluting beads. A cohort of 253 hepatocellular carcinoma patients who underwent 449 procedures of transarterial liver chemoembolization with drug-eluting beads using the Perclose Proglide device was prospectively studied. The main endpoints evaluated were the technical success of the device, defined as complete hemostasis achieved within 3 min after the closure, and the incidence of puncture-site complications. The secondary endpoints evaluated were the correlation between epidemiological factors, coagulation profile and degree of liver disease, and the occurrence of complications. Technical success was achieved in 96% of the cases. Among patients who underwent repeated procedures using the same vascular access, this rate was 95.3%. Puncture-site complications were observed in 7 procedures (1.56%); 4 (0.89%) were due to hemorrhage, 2 (0.44%) hematomas and 2 (0.44%) pseudoaneurysms; 2 (0.44%) due to limb ischemia; and 1 (0.22%) due to arterial dissection. Among them, 3 cases required intervention. The statistical analysis of demographic characteristics, Child-Pugh classification, and coagulation status did not show a significant correlation with the occurrence of complications. Of the 449 procedures, only 4 (0.89%) needed hospitalization due to puncture-site complications. The use of Perclose Proglide is safe and effective in patients with liver disease and hepatocellular carcinoma who underwent transarterial liver chemoembolization with drug-eluting beads.


Cone beam computed tomography evaluation of distance from cementoenamel junction to alveolar crest before and after nonextraction orthodontic treatment.
To evaluate the distance between the cementoenamel junction and the alveolar bone crest before and after orthodontic treatment using cone beam computed tomography (CBCT). The sample comprised 30 patients with Angle Class I malocclusion and mild to moderate crowding. The study database comprised dental CBCT scans obtained before and after orthodontic treatment. The distance between the cementoenamel junction to the bone crest of the buccal (n = 720) and lingual (n = 720) surfaces was measured in 24 teeth for each patient using a specific software tool (Xoran version 3.1.62). The Wilcoxon test was used for statistical analysis, and the level of significance was set at P < .05. The distance between the cementoenamel junction and the bone crest increased in 822 (57%) of the 1440 surfaces after orthodontic treatment. The buccal surface of the lower central incisors had the greatest frequency of increased distance (75%), and the lingual surface of lateral incisors had the lowest (40%). The distance between the cementoenamel junction and the alveolar bone crest was greater than 2 mm (alveolar bone dehiscence) in 162 (11%) of the 1440 surfaces before orthodontic treatment and in 279 (19%) after treatment. The distance from the cementoenamel junction to the bone crest changed after orthodontic treatment; the distance was greater than 2 mm in 11% of the surfaces before treatment and in 19% after treatment.


Hypomethylation of repetitive elements in blood leukocyte DNA and risk of gastric lesions in a Chinese population.
To explore the association between hypomethylation of repetitive elements (LINE-1, Sat2, and ALU) in blood leukocyte DNA and risks of gastric lesions, and development of gastric cancer (GC), a population-based study was conducted in a high-risk area of GC in China. Methylation levels were determined by MethyLight in 902 subjects with various gastric lesions from two cohort studies at baseline and 276 subjects with long-term follow-up data. The frequency of LINE-1 or Sat2 hypomethylation was significantly increased in subjects with dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. The odds ratios (ORs) were 2.22 [95% confidence interval (CI): 1.45-3.40] for LINE-1 and 1.58 (95% CI: 1.14-2.21) for Sat2. A dose-response pattern was found for the risk of DYS and LINE-1 hypomethylation (P-trend<0.001). Further stratified analysis indicated that the frequency of LINE-1 or Sat2 hypomethylation was higher in subjects with Helicobacter pylori infection. The ORs were 1.83 (95% CI: 1.12-2.99) for LINE-1 and 1.44 (95% CI: 1.01-2.05) for Sat2. The follow-up data indicated that the risk of progression to GC was increased in intestinal metaplasia (IM) subjects with LINE-1 hypomethylation (OR=2.82; 95% CI: 1.17-6.77) or Sat2 hypomethylation (OR=2.78; 95% CI: 1.15-6.74). The risk of progression to GC was also increased in DYS subjects with Sat2 hypomethylation (OR=5.24; 95% CI: 2.00-13.74). These findings suggest that hypomethylation of repetitive elements in blood leukocytes is associated with the risks of advanced gastric lesions and development of GC.


[Daily physical activity in adult patients with cystic fibrosis].
Assessment of daily physical activity (DPA) is a major element in the development of respiratory rehabilitation. The aim of this study was to evaluate the DPA and the daily energy expenditure (DEE) in adult patients with cystic fibrosis. Thirty adult patients (16 women, 14 men, mean age 27.1±8.4 years) with cystic fibrosis (FVC: 69.2±19%, FEV1: 55.1±24%, BMI: 20.5±3.6kg/m(2)), in stable condition were included in the study. The questionnaire allowed DPA to estimate DEE from the intensity and type of activity. This tool divides the DEE into four intensity levels: less than 1 Metabolic Equivalent Task (MET), greater than 1 and less than 3 METs, 3-5 METs, and greater than 5 METs. A shuttle test for estimating VO(2) peak was performed in all patients. The DEE reached 9478.4±3224.3kJ24h(-1) and was significantly and highly correlated with calculated peak VO(2) (l/min) (r=0.876, P=<0.001); 22% DEE was less than 3 METs, 10% between 3 and 5 METs et 2,5% greater than 5 METs; 65% DEE was less than 1 MET. There was a strong correlation between DEE and BMI (r=0.860, P=<0.001), a low correlation with FVC (r=0.423, P=0.02). This questionnaire is relevant for estimating DPA and DEE in patients with cystic fibrosis and is an interesting test to be used to evaluate changes in patients after pulmonary rehabilitation.


Association of Nutritional Support With Clinical Outcomes Among Medical Inpatients Who Are Malnourished or at Nutritional Risk: An Updated Systematic Review and Meta-analysis.
Malnutrition affects a considerable proportion of the medical inpatient population. There is uncertainty regarding whether use of nutritional support during hospitalization in these patients positively alters their clinical outcomes. To assess the association of nutritional support with clinical outcomes in medical inpatients who are malnourished or at nutritional risk. For this updated systematic review and meta-analysis, a search of the Cochrane Library, MEDLINE, and Embase was conducted from January 1, 2015, to April 30, 2019; the included studies were published between 1982 and 2019. A prespecified Cochrane protocol was followed to identify trials comparing oral and enteral nutritional support interventions with usual care and the association of these treatments with clinical outcomes in non-critically ill medical inpatients who were malnourished. Two reviewers independently extracted data and assessed risk of bias; data were pooled using a random-effects model. The primary outcome was mortality. The secondary outcomes included nonelective hospital readmissions, length of hospital stay, infections, functional outcome, daily caloric and protein intake, and weight change. A total of 27 trials (n = 6803 patients) were included, of which 5 (n = 3067 patients) were published between 2015 and 2019. Patients receiving nutritional support compared with patients in the control group had significantly lower rates of mortality (230 of 2758 [8.3%] vs 307 of 2787 [11.0%]; odds ratio [OR], 0.73; 95% CI, 0.56-0.97). A sensitivity analysis suggested a more pronounced reduction in the risk of mortality in recent trials (2015 or later) (OR, 0.47; 95% CI, 0.28-0.79) compared with that in older studies (OR, 0.94; 95% CI, 0.72-1.22), in patients with established malnutrition (OR, 0.52; 95% CI, 0.34-0.80) compared with that in patients at nutritional risk (OR, 0.85; 95% CI, 0.62-1.18), and in trials with high protocol adherence (OR, 0.67; 95% CI, 0.54-0.84) compared with that in trials with low protocol adherence (OR, 0.88; 95% CI, 0.44-1.76). Nutritional support was also associated with a reduction in nonelective hospital readmissions (14.7% vs 18.0%; risk ratio, 0.76; 95% CI, 0.60-0.96), higher energy intake (mean difference, 365 kcal; 95% CI, 272-458 kcal) and protein intake (mean difference, 17.7 g; 95% CI, 12.1-23.3 g), and weight increase (0.73 kg; 95% CI, 0.32-1.13 kg). No significant differences were observed in rates of infections (OR, 0.86; 95% CI, 0.64-1.16), functional outcome (mean difference, 0.32; 95% CI, -0.51 to 1.15), and length of hospital stay (mean difference, -0.24; 95% CI, -0.58 to 0.09). This study's findings suggest that despite heterogeneity and varying methodological quality among trials, nutritional support was associated with improved survival and nonelective hospital readmission rates among medical inpatients who were malnourished and should therefore be considered when treating this population.


Retracted: Clinical and Biological Significances of a Ferroptosis-Related Gene Signature in Lung Cancer Based on Deep Learning.
[This retracts the article DOI: 10.1155/2022/6495301.].


Is there any evidence to advocate SUI prevention in continent women undergoing prolapse repair? An overview.
Postoperative SUI prevention at the time of prolapse surgery is still a challenging issue. Recent findings suggested that a systematic prophylactic Burch colposuspension could be performed in continent women undergoing a sacral colpopexy. The aim of this paper is to collect relevant literature in order to suggest a management strategy. A thorough PubMed research of all papers in the English language was conducted. Evidence-based medicine was analyzed and current unanswered questions were discussed. Despite evident limitations, it appears to be some benefit from preoperative screening with a stress test during prolapse reduction. In continent patient with a positive stress test, adding a preventive procedure could be fully justified. In regard to contradictory published data, when negative stress test, patient counseling is important and the ratio of risk-benefit should be rigorously discussed. Further randomized controlled studies are needed to support either a prophylactic or a second-step strategy.


Immediate and long-term effects of testosterone on song plasticity and learning in juvenile song sparrows.
Steroid sex hormones play critical roles in the development of brain regions used for vocal learning. It has been suggested that puberty-induced increases in circulating testosterone (T) levels crystallize a bird's repertoire and inhibit future song learning. Previous studies show that early administration of T crystallizes song repertoires but have not addressed whether new songs can be learned after this premature crystallization. We brought 8 juvenile song sparrows (Melospiza melodia) into the laboratory in the late summer and implanted half of them with subcutaneous T pellets for a two week period in October. Birds treated with T tripled their singing rates and crystallized normal songs in 2 weeks. After T removal, subjects were tutored by 4 new adults. Birds previously treated with T tended toward learning fewer new songs post T, consistent with the hypothesis that T helps to close the song learning phase. However, one T-treated bird proceeded to learn several new songs in the spring, despite singing perfectly crystallized songs in the fall. His small crystallized fall repertoire and initial lag behind other subjects in song development suggest that this individual may have had limited early song learning experience. We conclude that an exposure to testosterone sufficient for crystallization of a normal song repertoire does not necessarily prevent future song learning and suggest that early social experiences might override the effects of hormones in closing song learning.


Amide-decorated carbon dots as sensitive and selective probes for fluorescence enhancement detection of cadmium ion.
As highly toxic metal ions, cadmium ions (Cd2+) are prevalent in varying concentrations around the world. The establishment of an accurate and effective method for Cd2+ determination with high sensitivity and selectivity is of particular concern. The present work fabricated a fluorescence chemosensor for the detection of Cd2+ based on functionalized carbon dots (CDs), which were hydrothermally prepared using amidated hyperbranched-polyethyleneimine (HPEI). As investigated by FTIR, NMR, and XPS, the stably grafted amide groups endowed the CDs with thermosensitivity and high cloud point due to the change in hydrophilic-hydrophobic behaviors. The CDs chemosensor with optimal amidation degree exhibited high sensitivity, selectivity, and stability in the determination of Cd2+ from various water environments. Notably, the fluorescence intensity enhanced with the increase of Cd2+ concentration, originating from the improved structure rigidity caused by the interactions between grafted amides and Cd2+. These impressive features made the CDs not only sensitive to detecting Cd2+ in low-concentration solutions with a limit of detection of 3.41 nM (the lowest known value for Cd2+ detection) but also accurate for the quantification in high-concentration solutions with a detectable Cd2+ concentration of 6.0 × 10-2 M. Owing to the broad detection range, the CDs developed in present work show great potential applications in various scenarios.


Effect of tandem repeats of antimicrobial peptide CC34 on production of target proteins and activity of Pichia pastoris.
Antimicrobial peptides (AMPs) are attracting attention in the fields of medicine, food, and agriculture because of their broad-spectrum antibacterial properties, low resistance, and low-residue in the body. However, the low yield and instability of the prepared AMP drugs limit their application. In this study, we designed a tetramer of the AMP CC34, constructed and transfected two recombinant expression vectors with pGAPZαA containing a haploid CC34 and tetraploid CC34 (CC34-4js) into Pichia pastoris to explore the effect of biosynthesized peptides. The results showed that CC34 and CC34-4js expression levels were 648.2 and 1105.3 mg/L, respectively, in the fermentation supernatant of P. pastoris. The CC34-4js tetramer showed no antibacterial activity, could be cleaved to the monomer using formic acid, and the hemolytic rate of the polyploid was slightly lower than that of monomeric CC34. The average daily gain, average daily feed intake, feed conversion ratio and immune organ index of rats fed CC34 and CC34-4js showed no differences. In conclusion, CC34-4js exhibited a higher yield and lower hemolysis in P. pastoris than those of CC34. Finally, CC34 and CC34-4js enterokinase lysates showed similar antibacterial activity and both expressed peptides potentially improved the growth performance and organ indices of rats.


Similar amino acid sequences revisited.
The rapid accumulation of protein sequences, many bearing unexpected resemblances to each other, is providing a new perspective on evolution.


Ductal Carcinoma In Situ: Treatment Update and Current Trends.
Ductal carcinoma in situ (DCIS) traditionally has been managed through various combinations of surgery, radiation, and endocrine therapy. However, concern for under- or over-treatment of DCIS has led many surgeons to question historically standardized approaches and instead begin to tailor treatment based on individual prognostic indicators. Recent and ongoing clinical trials have investigated the potential for active surveillance in DCIS, the possibility of eliminating radiation therapy (RT), and ways in which adjuvant systemic therapy may be refined. This review will summarize the current trends in the treatment of DCIS, as well as highlight the most pertinent clinical trials that are shaping management today.


[Intrauterine growth retardation, its consequences in infancy, in the child and long term].
The authors report the consequence of intra-uterine growth retardation on infancy and adult disease. During infancy in 7 to 10% of cases a growth retardation less than -2 DS, is observed and subsequently needs growth hormone treatment. In adult X syndrome (hypertension, diabetes of 2 types insulino resistant and cardiovascular disease) is observed 18 times more in subjects where the birth weight was low than 2.4 kg. Finally the authors give some recommendations to follow-up of the infants born with a growth restriction.


Scaffolds for bone restoration from cuttlefish.
Scaffolds of pure hydroxyapatite suitable for either direct clinical use or tissue-engineering applications were successfully produced via hydrothermal transformation of aragonite, obtained from fresh cuttlefish bones, at 200 degrees C followed by sintering. Beyond low production cost, worldwide availability and natural-biological origin of raw materials, the produced scaffolds have ideal pore size and interconnectivity features suitable for supporting biological activities, such as bone tissue growth and vascularization. Bioactivity in vitro tests were excellent: (a) rapid and pronounced formation of hydroxyapatite occurred when the scaffolds were immersed in simulated body fluid (SBF), and (b) outstanding proliferation of osteoblasts was registered. The produced scaffolds can be machined and shaped very easily at any stage of processing. Therefore, these ceramic scaffolds can satisfy both bioactivity demands and the requirements for shaping of tailor-made individualized implants, especially for randomly damaged bones.


Chronic Hepatitis C: Do Generics Work as Well as Branded Drugs?
India has a large share of the hepatitis C virus (HCV) burden of the world. Unsafe medical practices and blood transfusions are the leading modes of transmission of HCV in India. The commonest HCV genotype in India is genotype 3 followed by genotype 1. While directly acting antivirals (DAAs) agents have become available at reasonable rates in India, cost of therapy remains a major barrier for control of HCV in India. Generic DAAs have been proven to be cost-saving in prior studies. We examined data from various studies in India and elsewhere using generic DAAs, and evaluated whether they are equally efficacious as the branded drugs. Since the availability of generic DAAs in the Indian market, there is a lot of real life data as well as prospective studies in special patient populations such as hematological disorders (thalassemia and hemophilia), chronic kidney disease, hemodialysis patients, post liver and renal transplant patients on immunosuppression, intravenous drug users, confections and other high risk groups. Control of HCV infection in India requires multi pronged approach. There is a need to formulate a health educational curriculum targeting not only the high-risk population but also the general population regarding the transmission of HCV. Adopting the dual approach of treating the old cases (decreasing the reservoir pool of HCV) and decreasing the incidence of new ones would help curtail the disease and decrease liver related mortality. In this scenario, the role of efficacious low cost generic medications is essential.


Green extraction of lutein from marigold flower petals, process optimization and its potential to improve the oxidative stability of sunflower oil.
Marigold flower petals are considered the richest source of lutein which possesses immense applications in the food and health sector. The study was undertaken to improve the stability of sunflower oil by enriching it with lutein extracted from marigold flower petals using safe and green technology. The extraction of lutein was optimized using Box-Behnken design by ultrasound-assisted extraction (UAE) employing sunflower oil as a solvent. The impact of three independent variables i.e., ultrasonic intensity, solid to solvent ratio, and extraction time were evaluated on the amount of lutein extracted and its antioxidant activity. Highest amount of lutein (21.23 mg/g) was extracted by employing ultrasonic intensity of 70 W/m2, extraction time of 12.5 min, and solid to solvent ratio of 15.75%. FT-IR spectra of lutein extracted by ultrasound and conventional extraction show similar peaks depicting that ultrasound does not have any impact on the functionality of lutein. Sunflower oil incorporated with lutein at 1000 PPM and the synthetic antioxidant (TBHQ) showed good oxidative stability than oil with 500 PPM lutein and no lutein during accelerated storage for a month. The oxidative stability was shown by different oil samples in the following order: TBHQ = 1000PPM lutein˃500PPM lutein ˃control oil. It was concluded that the ultrasound technique extracts lutein efficiently from marigold flowers and this lutein was effective in improving the oxidative stability of sunflower oil under accelerated storage conditions.


Efficacy of oscillating rotating versus side-to-side powered toothbrushes on plaque and gingival index reduction: A systematic review.
The authors conducted a systematic review to assess the efficacy of oscillating rotating (OR) versus side-to-side (SS) powered toothbrushes on plaque and gingival index reduction. The authors searched 3 electronic databases and the gray literature for randomized clinical trials in which investigators compared OR with SS powered toothbrushes. Two authors independently screened the studies, performed data abstraction, and assessed the risk of bias. The authors used random-effects model meta-analyses to pool results across trials and the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of evidence. This systematic review included 24 trials in which researchers enrolled a total of 2,998 patients. There was moderate-certainty evidence that SS toothbrushes may result in little to no difference in plaque index reduction from baseline to 4 weeks compared with OR toothbrushes (standardized mean difference, 0.02; 95% confidence interval, -0.46 to 0.42). There was moderate-certainty evidence that SS toothbrushes may result in little to no difference in gingival index reduction from baseline to 4 weeks compared with OR toothbrushes (standardized mean difference, 0.13; 95% confidence interval, -0.47 to 0.22). There was moderate-quality evidence suggesting little to no difference in adverse events. The evidence does not suggest the superiority of either OR or SS toothbrushes for plaque or gingival index reduction. Clinicians and patients considering the use of either of these toothbrushes are unlikely to observe more benefits with one type versus the other.