Sialin expression in the CNS implicates extralysosomal function in neurons.
SLC17A5 encodes a lysosomal membrane protein, sialin, which transports sialic acid from lysosomes. Mutations in sialin result in neurodegenerative sialic acid storage disorders, Salla disease (SD) and infantile sialic acid storage disease (ISSD). Here we analyzed sialin in mouse central nervous system (CNS) and primary cortical and hippocampal neurons and glia. In the CNS, sialin was predominantly expressed in neurons, especially in the proliferative zone of the prospective neocortex and the hippocampus in developing brain. In nonneuronal cells and primary glial cell cultures, mouse sialin was localized into lysosomes but interestingly, in primary neuronal cultures sialin was not targeted into lysosomes but rather revealed a punctate staining along the neuronal processes and was also seen in the plasma membrane. These data demonstrate a nonlysosomal localization of sialin in neurons and would imply a role for sialin in the secretory processes of neuronal cells.


Behavioral and gene expression analyses of Wfs1 knockout mice as a possible animal model of mood disorder.
Wolfram disease is a rare genetic disorder frequently accompanying depression and psychosis. Non-symptomatic mutation carriers also have higher rates of depression and suicide. Because WfS1, the causative gene of Wolfram disease, is located at 4p16, a linkage locus for bipolar disorder, mutations of WfS1 were suggested to be involved in the pathophysiology of bipolar disorder. In this study, we performed behavioral and gene expression analyses of Wfs1 knockout mice to assess the validity as an animal model of mood disorder. In addition, the distribution of Wfs1 protein was examined in mouse brain. Wfs1 knockout mice did not show abnormalities in circadian rhythm and periodic fluctuation of wheel-running activity. Behavioral analysis showed that Wfs1 knockout mice had retardation in emotionally triggered behavior, decreased social interaction, and altered behavioral despair depending on experimental conditions. Wfs1-like immunoreactivity in mouse brain showed a similar distribution pattern to that in rats, including several nuclei potentially relevant to the symptoms of mood disorders. Gene expression analysis showed down-regulation of Cdc42ep5 and Rnd1, both of which are related to Rho GTPase, which plays a role in dendrite development. These findings may be relevant to the mood disorder observed in patients with Wolfram disease.


Electrospinning of zein-ethyl cellulose hybrid nanofibers with improved water resistance for food preservation.
Zein electrospun nanofibers have poor water resistance, which restricts its applications in food preservation. To improve the water resistance of nanofibers, zein/ethyl cellulose (EC) hybrid nanofibers were prepared at different ratios. Besides, we also encapsulated cinnamon essential oil (CEO) into electrospun fibers for Agaricus bisporus preservation. As the weight ratio of EC increased from 0% (ZE-10) to 100% (ZE-01), the viscosity of electrospinning solutions gradually increased from 80.33 ± 19.23 mPa·s to 756.78 ± 22.48 mPa·s, resulting in sufficient chain entanglement for the preparation of uniform fibers. The average diameters of ZE-01, ZE-12, ZE-11, ZE-21, and ZE-10 nanofibers were 326 ± 53 nm, 267 ± 31 nm, 237 ± 51 nm, 292 ± 45 nm, and 362 ± 70 nm, respectively. The hydrogen bonds between the hydroxyl groups of ethyl cellulose and the amino groups of zein decreased the amount of free hydrophilic group, thus improving water resistance of nanofibers. Food packaging potential was evaluated using Agaricus bisporus. The zein/EC nanofibers loaded CEO significantly decreased weight loss and maintained the firmness of the Agaricus bisporus, and improved the quality of the Agaricus bisporus during storage.


Exocrine pancreatic function in hepatocyte nuclear factor 1β-maturity-onset diabetes of the young (HNF1B-MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas.
To examine the exocrine pancreatic function in carriers of the hepatocyte nuclear factor 1β gene (HNF1B) mutation by direct testing. Patients with HNF1B mutations and control subjects were assessed using rapid endoscopic secretin tests and secretin-stimulated magnetic resonance imaging. Seven patients and 25 controls underwent endoscopy, while eight patients and 20 controls had magnetic resonance imaging. Ductal function was assessed according to peak bicarbonate concentrations and acinar function was assessed according to peak digestive enzyme activities in secretin-stimulated duodenal juice. The association of pancreatic exocrine function and diabetes status with pancreatic gland volume was examined. The mean increase in secretin-stimulated duodenal fluid was smaller in patients than controls (4.0 vs 6.4 ml/min; P = 0.003). We found lower ductal function in patients than controls (median peak bicarbonate concentration: 73 vs 116 mEq/L; P < 0.001) and lower acinar function (median peak lipase activity: 6.4 vs 33.5 kU/ml; P = 0.01; median peak elastase activity: 0.056 vs 0.130 U/ml; P = 0.01). Pancreatic fluid volume outputs correlated significantly with pancreatic gland volumes (r² = 0.71, P = 0.008) in patients. The total fluid output to pancreatic gland volume ratios were higher in patients than controls (4.5 vs 1.3 ml/cm³; P = 0.03), suggesting compensatory hypersecretion in the remaining gland. Carriers of the HNF1B mutation have lower exocrine pancreatic function involving both ductal and acinar cells. Compensatory hypersecretion suggests that the small pancreas of HNF1B mutation carriers is attributable to hypoplasia, not atrophy.


Sleep disturbance in alopecia areata: A cross-sectional study.
Alopecia areata (AA) is a nonscarring hair loss with autoimmune pathophysiology, which is associated with psychiatric disorders including anxiety and depression. Sleep disorders are commonly seen with anxiety and depression. Here we evaluate the sleep quality of AA patients. This cross-sectional study involved 51 AA patients and 51 age- and sex-matched healthy controls. The sleep quality and day sleepiness were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires. The severity of AA was evaluated with the Severity of Alopecia Tool (SALT). Unlike the ESS score, the mean PSQI score was significantly higher in the AA group compared with the controls (7 ± 4.13 vs. 3.53 ± 1.96, p < 0.001). The number of cases with ESS ≥ 11, indicating the excess daytime sleepiness, was significantly higher in the AA group compared with controls (15 vs. 6, p = 0.02). There was no significant correlation between PSQI score and age, age of onset of the disease, or SALT score (p > 0.05). Anxiety and depression were more common in the AA group versus controls (p = 0.9). PSQI score was higher in AA patients who had anxiety and depression compared with those who did not (9.9 ± 5.28 vs. 4.76 ± 3.08, p = 0.001). Sleep quality is impaired in AA patients. As expected, sleep would be more disturbed in AA cases with depression or anxiety. Therefore, attention to sleep quality and concomitant psychiatric diseases is essential in AA clinical management.


In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation.
This study describes the in-situ gelling of econazole nitrate containing thermosensitive polymers composed of poloxamer 407 and 188 as a novel treatment platform for vaginal candidiasis. Aqueous thermosensitive formulations containing 1% of econazole nitrate and poloxamer 407 and/or 188 were prepared and their rheological, mechanical and drug-release properties determined at 20 ± 0.1°C and/or 37 ± 0.1°C. Based on their biologically suitable thermorheological properties, formulations containing the mixtures of poloxamer 407 and 188 in ratios of 15:15 (F1), 15:20 (F2) and 20:10 (F3) were chosen for comprehensive analysis. Formulations based on F3 exhibited typical gel-type mechanical spectra (G' > G″) at 37°C whereas formulations based on F1 and F2 exhibited properties akin to weakly cross-linked gels. Texture profile analysis demonstrated that F3 showed the highest cohesiveness, adhesiveness, hardness and compressibility. No statistically significant differences (P > 0.5) were observed in the release of econazole nitrate from the formulations at pH 4.5, which in all cases followed anomalous diffusion kinetics. Formulations based on 20% poloxamer 407:10% poloxamer 188 were chosen for in-vivo studies and were shown to be effective for the treatment of the vaginal candidiasis. Histopathologic evaluation also supported the effectiveness of the thermosensitive formulation administered intravaginally. By careful engineering of the rheological properties, in-situ thermosensitive gel formulations of econazole nitrate were prepared and were shown to be efficacious in the treatment of vaginal candidiasis.


Zr61Ti2Cu25Al12 metallic glass for potential use in dental implants: biocompatibility assessment by in vitro cellular responses.
In comparison with titanium and its alloys, Zr61Ti2Cu25Al12 (ZT1) bulk metallic glass (BMG) manifests a good combination of high strength, high fracture toughness and lower Young's modulus. To examine its biocompatibility required for potential use in dental implants, this BMG was used as a cell growth subtract for three types of cell lines, L929 fibroblasts, human umbilical vein endothelial cells (HUVEC), and osteoblast-like MG63 cells. For a comparison, these cell lines were in parallel cultured and grown also on commercially pure titanium (CP-Ti) and Ti6-Al4-V alloy (Ti64). Cellular responses on the three metals, including adhesion, morphology and viability, were characterized using the SEM visualization and CCK-8 assay. Furthermore, real-time RT-PCR was used to measure the activity of integrin β, alkaline phosphatase (ALP) and type I collagen (COL I) in adherent MG63 cells. As indicated, in all cases of three cell lines, no significant differences in the initial attachment and viability/proliferation were found between ZT1, CP-Ti, and Ti64 until 5d of incubation period. It means that the biocompatibility in cellular response for ZT1 BMG is comparable to Ti and its alloys. For gene expression of integrin β, ALP and COL I, mRNA level from osteoblast cells grown on ZT1 substrates is significantly higher than that on the CP-Ti and Ti64. It suggests that the adhesion and differentiation of osteoblasts grown on ZT1 are even superior to those on the CP-Ti and Ti64 alloy, then promoting bone formation. The good biocompatibility of ZT1 BMG is associated with the formation of zirconium oxide layer on the surface and good corrosion-resistance in physiological environment.


XBP1s gene of endoplasmic reticulum stress enhances proliferation and osteogenesis of human periodontal ligament cells.
The endoplasmic reticulum stress (ERS) pathway, inositol-requiring enzyme-1 alpha-X-box binding protein-1 (IRE1α-XBP1), has been considered as a critical factor of human periodontal ligament cells (hPDLCs) in proliferation and osteogenesis. This study aimed to explore the effect and mechanism of XBP1s, which was cleaved by IRE1α on the proliferation and osteogenesis of hPDLCs. ERS model was induced by tunicamycin (TM); cell proliferation was assessed by CCK-8 assay; pLVX-XBP1s-hPDLCs cell line was established by lentivirus infaction; expression of ERS-related protein including eIF2α, GRP78, ATF4 and XBP1s, autophagy-related P62 and LC3, and apoptosis-related Bcl-2 and Caspase-3 were detected by Western Blot; expression of osteogenic genes was detected by RT-qPCR, and senescence of hPDLCs was explored by β-galactosidase staining. Furthermore, the interaction between XBP1s and human bone morphogenetic protein 2 (BMP2) was examined by immunofluorescence antibody test (IFAT). The results showed an increase in proliferation of hPDLCs from 0 to 24 h when ERS was induced by TM treatment (P < 0.05). XBP1s overexpression induced hPDLCs proliferation, upgraded autophagy and degraded apoptosis significantly (P < 0.05). In pLVX-XBP1s-hPDLCs, the ratio of senescent cells was markedly decreased after several passages (P < 0.05); After infection with pLVX-BMP2 lentiviral supernatant, IFAT result showed that XBP1s and BMP2 well co-located in the cytoplasm of pLVX-XBP1s-hPDLCs and PERK-ATF4 ERS branch was activated, meanwhile, there were obviously more mineralized nodules and mRNA expression of osteogenesis-related genes was continually up-regulated (P < 0.05). XBP1s promotes the proliferation via regulating the autophagy and apoptosis, and enhances expression of osteogenic genes in hPDLCs. The mechanisms in this regard need exploring further for periodontal tissue regeneration, functionalization and clinical applications.


"Caught in the Act" @ disruption of A-ET-E process in the recognition of F- by a lamellar EuIII-MOF in heterogeneous manner with logic gate construction: From protagonist idea to implementation world.
Development of cost-effective and reliable fluoride sensor for assessing water quality of natural water samples is of immense importance in developing countries as they can provide an easy platform for safeguarding human health. These sensors should be as simple as possible to be fabricated locally by layman. In this context, EuIII-based MOFs provide trustable platform with bright luminescence in the visible region due to their absorbance-energy transfer-emission (A-ET-E) process. Herein the designed synthesis of a 2D porous coordination polymer, Eu@CMERI, has been carried out following a solvothermal reaction route. The compound shows selective "turn-off" sensing of fluoride in heterogeneous manner from purely aqueous phase and other biological matrices with a detection limit of 28.4 ppb and it carries enormous importance for drinking water analysis under internal regulations. Prohibition of A-ET-E cycle of the EuIII-MOF is proposed to be the prime reason for fluorescence quenching upon interaction with F-. DFT studies also revealed that lowest △EHOMO-LUMO and highest chemical potential value (μ) of F- are the driving forces for selectivity of EuIII-MOF towards the targeted anion. The high stability of the porous frameworks along with its interesting sensing features, including fast response and wide linear detection range etc. instigated us not to restrict the chemistry of EuIII-MOFs at protagonist idea rather to explore its application to real-world analysis. Based on the fluorescence signal exhibited by the targeted analyte, an integrated AND-OR logic gate has also been fabricated which depicts its applicability in molecular electronics. In view of the modular design principle of our polymeric probe, the proposed strategy could open a new horizon to construct powerful sensing materials for ultrafast detection of other important pollutants in the domain of supramolecular chemistry in coming days.


Master of mimicry: Rare primary cutaneous anaplastic large cell lymphoma presenting as fungating parotid tumor-case report and review.
Primary cutaneous anaplastic large cell lymphomas (PC-ALCL) are rare. They fall within non-Hodgkin's lymphomas spectrum. Commonly misdiagnosed, this malignancy involving the skin has favorable prognosis. To the best of our knowledge, this is the first reported case of PC-ALCL involving the parotid gland. This clinical presentation can mislead surgeons. We highlight this diagnostic conundrum. A 73-year-old gentleman presented with two painless, ulcerating nodules over the right pre-auricular and angle of the mandible. Prior to that, he had right pre-auricular swelling that enlarged over a year. Skin nodules erupted few weeks before seeking treatment. Computed Tomography scan reported homogenously enhancing masses at posterior part of parotid gland's superficial lobe with diffuse lobe enlargement and no regional lymphadenopathy. A hypodense lesion at the liver indicated metastasis. Biopsy revealed PC-ALCL. He responded well to chemotherapy. PC-ALCL commonly presents as solitary nodules that can ulcerate over the head and neck region. Reports of PC-ALCL involving the eyelids, lips, and breast were found in our literature review. Multifocal lesions occur in 20% of cases. Malignant parotid tumors are aggressive and require parotidectomy which carry the risk of facial nerve injury. Treatment of PC-ALCL however, is local excision and radiotherapy for solitary lesions; and chemotherapy for those with extracutaneous spread. The 5-year survival rate is 90% in PC-ALCL. PC-ALCL is a master of mimicry. To prevent serious morbidity, awareness regarding this entity as a differential diagnosis compared to the common malignant parotid tumors need to be raised.


Family needs of critically ill patients in the emergency department.
Family members' experience a range of physiological, psychological and emotional impacts when accompanying a critically ill relative in the emergency department. Family needs are influenced by their culture and the context of care, and accurate clinician understanding of these needs is essential for patient- and family-centered care delivery. The aim of this study was to describe the needs of Taiwanese family members accompanying critically ill patients in the emergency department while waiting for an inpatient bed and compare these to the perceptions of emergency nurses. A prospective cross-sectional survey was conducted in a large medical center in Taiwan. Data were collected from 150 family members and 150 emergency nurses who completed a Chinese version of the Critical Care Family Needs Inventory. Family members ranked needs related to 'communication with family members,' as most important, followed by 'family member participation in emergency department care', 'family member support' and 'organizational comfort'; rankings were similar to those of emergency nurses. Compared to nurses, family members reported higher scores for the importance of needs related to 'communication with family members' and 'family members' participation in emergency department care'. Family members place greater importance than emergency nurses on the need for effective communication.


Effects of psychotropic drugs on pressor and behavioral responses to brain stimulation in unrestrained, unanesthetized rats.
Electrical stimulation of the posterior hypothalamus (PH) and the mesencephalic reticular formation (MRF) in unanesthetized, unrestrained rats with chronic electrode implants and an arterial cannula elicited a rise in blood pressure accompanied by behavioral changes such as exploration, flight or escape responses. Pentobarbital inhibited both the pressor and behavioral responses to PH and MRF stimulation. Chlorpormazine, diazepam and imipramine depressed the pressor response to PH stimulation rather than that to MRF stimulation with affecting the behavioral responses. It is concluded from these results that chlorpromazine, diazepam and imipramine exert their action on the neural pathway involved in the pressor response rather than on that inducing behavioral responses, whereas pentobarbital affects more extended brain areas related to these neural systems.


Bioinformatic analysis of the effect of SNPs in the pig TERT gene on the structural and functional characteristics of the enzyme to develop new genetic markers of productivity traits.
Telomerase reverse transcriptase (TERT) plays a crucial role in synthesizing telomeric repeats that safeguard chromosomes from damage and fusion, thereby maintaining genome stability. Mutations in the TERT gene can lead to a deviation in gene expression, impaired enzyme activity, and, as a result, abnormal telomere shortening. Genetic markers of productivity traits in livestock can be developed based on the TERT gene polymorphism for use in marker-associated selection (MAS). In this study, a bioinformatic-based approach is proposed to evaluate the effect of missense single-nucleotide polymorphisms (SNPs) in the pig TERT gene on enzyme function and structure, with the prospect of developing genetic markers. A comparative analysis of the coding and amino acid sequences of the pig TERT was performed with corresponding sequences of other species. The distribution of polymorphisms in the pig TERT gene, with respect to the enzyme's structural-functional domains, was established. A three-dimensional model of the pig TERT structure was obtained through homological modeling. The potential impact of each of the 23 missense SNPs in the pig TERT gene on telomerase function and stability was assessed using predictive bioinformatic tools utilizing data on the amino acid sequence and structure of pig TERT. According to bioinformatic analysis of 23 missense SNPs of the pig TERT gene, a predictive effect of rs789641834 (TEN domain), rs706045634 (TEN domain), rs325294961 (TRBD domain) and rs705602819 (RTD domain) on the structural and functional parameters of the enzyme was established. These SNPs hold the potential to serve as genetic markers of productivity traits. Therefore, the possibility of their application in MAS should be further evaluated in associative analysis studies.


Data analysis technique influences blood flow kinetics parameter estimates for moderate- and heavy-intensity exercise transitions.
What is the central question of this study? During exercise, there are fluctuations in conduit artery blood flow (BF) caused by both cardiac and muscle contraction-relaxation cycles. What is the optimal method to process Doppler ultrasound-measured BF for the purpose of characterizing the dynamic response of BF during step-transitions in exercise? What is the main finding and its importance? Continuous BF data were processed in relation to either cardiac or muscle contraction-relaxation cycles and computed based on 'binned' or 'rolling' averages over one, two or five consecutive cycles. Kinetics characterization revealed no data processing technique-specific differences in steady-state BF, but variability in the rapidity at which BF attained steady-state (i.e., mean response time) was observed. The overall rate of blood flow (BF) adjustment (i.e., kinetics) from the onset of an exercise transition can be quantified by the mean response time (MRT). However, the BF response profile can be distorted during rhythmic, dynamic exercise consequent to variations caused by the cardiac cycle (HR) and the muscle contraction-relaxation (CR) cycle. We examined the extent to which distortions imposed by HR and CR cycles affected BF kinetics. Eight healthy, young men (27 (4) years; mean (SD)) performed transitions of alternate-leg knee-extension exercise from 3 W to either a moderate- (MOD) or heavy-intensity (HVY) power output. Femoral artery BF was continuously measured by Doppler ultrasound and averaged over one, two or five 'binned' (e.g., HR2b, etc.) or 'rolling' (e.g., CR5r, etc.) HR and CR cycles. Among analysis techniques, there were no differences for steady-state BF values at the 3 W baseline. In MOD, MRT using contraction-relaxation cycle (CR1) was smaller than most other analysis techniques. For both MOD and HVY, the 95% confidence interval for MRT was generally larger when using HR- compared to CR-related methods, and monoexponential fits based on 'rolling' averages (HR2r, HR5r, CR2r, CR5r) had a poorer ability to estimate the true end-exercise BF in HVY than in MOD. When modelling BF kinetics, we conclude that the CR1 method is a good option because of its ability to accurately estimate the 'data-determined' end-exercise BF value from the 'model-derived' response, maintain a relatively high density of data points during the transition and yield a relatively small 95% CI.


First degree family history of diabetes and risk factors for cardiovascular disease in non-diabetic subjects in the National Telephone Company: a metabolic survey.
The effect of first degree family history of diabetes on known risk factors for cardiovascular disease was evaluated in 4989 non-diabetic employees of the Italian Telephone Company. Family history of diabetes was present in 759 subjects (476 males and 283 females); in these subjects body mass index, diastolic blood pressure, blood glucose levels (fasting and one and two-hour post-load), triglyceride and cholesterol levels were significantly higher than in age and sex-matched controls. In different age groups (less than 30, 31-40, 41-50, greater than 50 years) the effect of first degree family history of diabetes was evaluated after stratification by sex. In males with first degree family history of diabetes, this effect was strongest in the under 30 age group: body mass indices, systolic and diastolic blood pressures, fasting and two-hour post-load blood glucose levels, triglyceride and cholesterol levels were all significantly higher than in subjects with negative family history of diabetes. These differences between subjects with negative and positive family histories declined with age and disappeared in subjects over 50. In females the effect of familial diabetes was weaker and delayed for body mass index and one hour blood glucose, appearing only in subjects over 30. Multiple logistic analysis indicated that only body mass index and one-hour blood glucose levels were independently associated with positive family history of diabetes. The differences observed between males and females in the youngest age group were also confirmed by this analysis. These data may indicate a multifactorial genetic link leading to increased cardiovascular morbidity in subjects with diabetes.


Polyelectrolyte Membrane with Hydroxyapatite and Silver Nanoparticles as a Material for Modern Wound Dressings.
Modern wound dressings not only play a covering role but also facilitate the function of the wound, contributing to a faster healing process. In this paper, we present a polyelectrolyte system with nanosized elements that could stimulate the growth of eukaryotic cells while providing antimicrobial properties, which may be recommended as a potential dressing material. The proposed platform consisted of polyethyleneimine, hydroxyapatite, and silver nanoparticles and was characterized using various macroscopic techniques. The constructed membrane scaffold was evaluated with immobilized WEHI 164 cells as a model system for cells sustained at the interface of bone and skin. Moreover, the bacteriostatic function of the designed membrane material was evaluated using different bacterial strains.


The effect of different combinations of lignocaine, ketoprofen, xylazine and tolazoline on the acute cortisol response to dehorning in calves.
The aims of this study were (a) to evaluate the effect of xylazine and tolazoline, with and without lignocaine, on the cortisol response of calves following amputation dehorning and (b) to assess the effect of a non-steroidal anti-inflammatory drug (ketoprofen) and local anaesthesia on the cortisol response of calves to amputation dehorning. Plasma cortisol concentrations were measured in 100 dehorned or non-dehorned 3-month-old calves over an 8-h period following five different sedative/analgesic or control treatments. Sedative/analgesic treatments were: control (no anaesthesia); local anaesthesia and ketoprofen; local anaesthesia and xylazine; local anaesthesia, xylazine and tolazoline; and xylazine only. Within each sedative/analgesic treatment group, half the calves (n=10 per group) were amputation dehorned and half were not dehorned. The change in plasma cortisol concentrations in calves dehorned after being given ketoprofen and local anaesthesia did not differ significantly from that of non-dehorned control calves for at least 8 h. In contrast, the cortisol response of dehorned calves not given analgesic drugs peaked 30 min after dehorning and lasted >4 h. Xylazine injected before dehorning significantly reduced but did not eliminate the peak of the cortisol response. When both xylazine and local anaesthesia were administered before dehorning the peak in the cortisol response was virtually eliminated. In the dehorned calves that received xylazine with or without local anaesthesia, cortisol concentration increased significantly 3 h after dehorning and did not return to baseline until at least 5 h later. When tolazoline was administered shortly after xylazine, it caused a marked cortisol response, higher than the response to any other treatment. Combining ketoprofen and local anaesthesia minimised the cortisol response, and by inference the pain-induced distress, following amputation dehorning in calves. Xylazine reduced the initial cortisol response to dehorning but not as much as when local anaesthesia was also given. The increase in cortisol concentration from 3-8 h after dehorning in calves given xylazine alone or in combination with local anaesthesia suggests that calves experienced pain-induced distress during this time and that xylazine had no long-term analgesic effect. Tolazoline, used to reverse the sedative effects of xylazine, caused a marked cortisol response in calves via a mechanism which remains unclear.


Weight Stigma Among Sexual Minority Adults: Findings from a Matched Sample of Adults Engaged in Weight Management.
Despite elevated rates of obesity among some groups of sexual minority (SM) adults, research examining weight stigma in this population is scarce. Weight stigma and weight-related health correlates were assessed in SM adults (N = 658) versus heterosexual adults (N = 658) matched on sex, race/ethnicity, age, education, and BMI. Adults enrolled in WW (formerly Weight Watchers) completed digital questionnaires assessing experienced weight stigma, weight bias internalization (WBI), weight cycling, eating self-efficacy, eating to cope, physical activity, and health-related quality of life (HRQOL). Survey response rates ranged from 0.8% to 3.5%. There were no differences in experienced weight stigma between SM and heterosexual participants; more than two-thirds experienced weight stigma, and more than 50% reported stigma from family, health care providers, teachers and classmates, and community members. Gay men endorsed higher WBI than heterosexual men (β = 0.22, P < 0.001). Regardless of sexual orientation, WBI was associated with poorer mental HRQOL, lower eating self-efficacy, and increased eating to cope, controlling for demographics and BMI. Experiencing weight stigma is as common for SM adults as heterosexual adults engaged in weight management, and WBI is associated with maladaptive eating behaviors and poor mental HRQOL. Increased attention to weight stigma and its health implications in SM populations is warranted.


Tropane and ergot alkaloids in grain-based products for infants and young children in the Netherlands in 2011-2014.
An LC-MS/MS multi-method was developed to simultaneously quantify ergot alkaloids (EAs) and tropane alkaloids (TAs) in 113 cereal-based food for infants and young children. To assess yearly variation, samples were collected in 2011, 2012 and 2014. EAs were detected in 54% and TAs in 22% of the samples. Mean EA levels in the three sampling years were 10.6, 6.2 and 8.6 µg kg(-1), respectively (maximum: 115.4 µg kg(-1)), indicating that exposure to EAs would not have exceeded the health-based guidance values set by EFSA in 2012. Mean TA levels were 3.9, 2.4 and 0.4 µg kg(-1), respectively (maximum: 80.8 µg kg(-1)). The acute reference dose for TAs, derived by EFSA in 2013, would have been exceeded by young children when consuming some of the products sampled in 2011-2012. TA levels had decreased drastically in 2014, possibly due to measures taken by producers as response to the EFSA Opinion.


Expression of developmental genes during early embryogenesis of Hydra.
Hydra is a classical model to study key features of embryogenesis such as axial patterning and stem cell differentiation. In contrast to other organisms where these mechanisms are active only during embryonic development, in Hydra they can be studied in adults. The underlying assumption is that the machinery governing adult patterning mimics regulatory mechanisms which are also active during early embryogenesis. Whether, however, Hydra embryogenesis is governed by the same mechanisms which are controlling adult patterning, remains to be shown. In this paper, in precisely staged Hydra embryos, we examined the expression pattern of 15 regulatory genes shown previously to play a role in adult patterning and cell differentiation. RT-PCR revealed that most of the genes examined were expressed in rather late embryonic stages. In situ hybridization, nuclear run-on experiments, and staining of nucleolar organizer region-associated proteins indicated that genes expressed in early embryos are transcribed in the engulfed "nurse cells" (endocytes). This is the first direct evidence that endocytes in Hydra not only provide nutrients to the developing oocyte but also produce maternal factors critical for embryogenesis. Our findings are an initial step towards understanding the molecular machinery controlling embryogenesis of a key group of basal metazoans and raise the possibility that in Hydra there are differences in the mechanisms controlling embryogenesis and adult patterning.


Human IgG antibodies to carbohydrate and protein antigens in mouse protection tests with group B streptococci.
The protective effect of four commercial human gammaglobulin batches (I-IV) in mice was studied using six different strains of group B streptococci (GBS): types Ia; Ib; II, R-protein negative (R-); II, R+; III, R-; and III, R+. Each mouse received 1.0 ml gammaglobulin and 0.5 ml bacteria, 10(6)-10(8) colony forming units (CFU). There was a close correlation between antibody levels measured by the use of radiolabeled protein A and the mouse-protective effect of the gamma-globulins. The mouse-protection tests demonstrated that batch I protected against GBS types Ia and III, R- at low concentration (65 mg/kg mouse weight), against type Ib at medium (260 mg/kg) and against type III, R+ at high concentration. Batch IV protected against types Ia and Ib, although the doses were four times higher than those in batch I, but did not protect against type III, R+. There was no mouse protection by any of the batches against type II. Antibody levels against Ibc and R, protein antigens, were substantially lower in batch IV. Because the results of these mouse-protection studies indicate the importance of such antibodies against protein antigens, batches I-III might be more useful for therapy of neonatal GBS-septicemia.


A naturally DNase-free CRISPR-Cas12c enzyme silences gene expression.
Used widely for genome editing, CRISPR-Cas enzymes provide RNA-guided immunity to microbes by targeting foreign nucleic acids for cleavage. We show here that the native activity of CRISPR-Cas12c protects bacteria from phage infection by binding to DNA targets without cleaving them, revealing that antiviral interference can be accomplished without chemical attack on the invader or general metabolic disruption in the host. Biochemical experiments demonstrate that Cas12c is a site-specific ribonuclease capable of generating mature CRISPR RNAs (crRNAs) from precursor transcripts. Furthermore, we find that crRNA maturation is essential for Cas12c-mediated DNA targeting. These crRNAs direct double-stranded DNA binding by Cas12c using a mechanism that precludes DNA cutting. Nevertheless, Cas12c represses transcription and can defend bacteria against lytic bacteriophage infection when targeting an essential phage gene. Together, these results show that Cas12c employs targeted DNA binding to provide antiviral immunity in bacteria, providing a native DNase-free pathway for transient antiviral immunity.


Giant pancreatic insulinoma. The bigger the worse? Report of two cases and literature review.
Giant pancreatic insulinomas are rare endocrine tumors. We describe 2 cases reviewing the current literature. We report herein 2 female patients affected by giant insulinomas of 14cm and 6cm, respectively. Symptomatic hypoglycemia episodes occurred during 4 months in first case and 3 years in the second one until diagnosis. Both patients were successfully treated performing a distal pancreatectomy with splenic preservation in the first case and a Whipple's procedure in the second one. Up to now only 7 cases have been reported previously. Insulinomas larger than 3cm accounts for less than 5% of all. This literature review shows that despite the size hypoglycemic symptoms varies from 1 day to 3 years and only 1 out of 9 cases reported presented lymph nodes metastases. No recurrences have been described. One of the cases here described (14cm) is the largest presented in the literature. Despite the size, giant insulinoma is related apparently neither to metastases nor to the recurrences.


Cardiovascular morbidities in postoperative colorectal cancer patients.
This retrospective observational study investigated the long-term prevalence of new-onset cardiovascular disease (CVD) and the predictive role of atherosclerotic plaque in the aorta and iliac arteries for CVD in postoperative colorectal cancer (CRC) patients who received surgical treatment between 2014 and 2015. CVD included coronary or cerebrovascular diseases which required treatment and new-onset CVD included peri-and postoperatively diagnosed CVDs or aggravated CVDs that required additional treatment during follow-up. Of the 2,875 patients included in this study, the prevalence of CVD was 8.9% (255/2875) and 141 (4.9%) developed new-onset CVD. Maximum arterial stenosis in the aorta or iliac arteries occurred in 40.8 ± 18.6% of patients with new-onset CVD and 11.6 ± 13.8% of patients without new-onset CVD (p < 0.001). The mean new-onset CVD-free survival time in patients with > 30% and < 30% stenoses were 52.5 [95% confidence intervals (CIs) 50.0-54.9] and 66.5 (95% CIs 66.2-66.8) months, respectively (p < 0.001). The area under the receiver operating characteristic curve of the maximal arterial stenosis for new-onset CVD was 0.911. These results suggest that CRC patients are at risk for developing new-onset CVD, which is associated with reduced survival. Atherosclerotic burden in the aorta or both iliac arteries may help predict future CVD events.


Tripeptide, Arg-Gly-Asp, inhibits the transfection of protein-linked DNA of bacteriophage M2.
The effect of tripeptide, Arg-Gly-Asp (RGD), on the transfection activity of Bacillus phage M2 DNA was examined. The transfection activity decreased when M2 DNA was preincubated with RGD before it was added to competent cells.


YouTube as a source for information on newborn male circumcision: Is YouTube a reliable patient resource?
YouTube is the most popular open access media-sharing platform and is the second most visited websites worldwide. However, due to a lack of peer-review, YouTube is largely unregulated and can be susceptible to the spread of biased or misleading information. To evaluate the quality and potential bias of videos pertaining to newborn male circumcision (NMC) on YouTube. A YouTube search was performed on August 27, 2021 using the search term 'circumcision', and the top 100 videos were analyzed by two independent reviewers. Videos were categorized into groupings based on their source, and each video was evaluated for bias and was determined to be either pro-circumcision, anti-circumcision or neutral. Video quality was assessed using the DISCERN instrument (1-5 scale) and the Global Quality Scale (GQS) (1-5 scale). Video popularity was measured using the video power index (VPI). We found that the overall quality of videos on YouTube pertaining to NMC is generally low (DISCERN: 2.9 ± 0.7, GQS: 2.9 ± 1.1). When describing potential bias, 56% of videos were neutral and 44% were biased, of which 30% being anti-circumcision and 14% being pro-circumcision. Videos which were neutral, produced by health channels, or which featured physicians were associated with the highest quality ratings. However, when correlating total video views and likes with our quality assessments, we observed a significant negative correlation between the overall popularity of a video and its DISCERN (ρ = -0.297, p = 0.031) and GQS quality ratings (ρ = -0.274, p = 0.048). Information pertaining to NMC on YouTube is generally of low quality and has a high potential for bias. Lower quality content is overrepresented on YouTube and tended to be more popular than higher quality content. Patients and their families should be cautious when accessing YouTube for health information pertaining to NMC.


Postoperative atrial fibrillation in noncardiothoracic surgical patients.
Atrial fibrillation is a common arrhythmia whose prevalence increases with age. It is a well-known complication of cardiothoracic surgery, but the incidence and contributing factors to the development of atrial fibrillation in noncardiothoracic surgical patients are less well known. This study was undertaken to investigate the incidence, association with known risk factors, treatment, and outcome of atrial fibrillation in postoperative noncardiac, nonthoracic surgical patients. A 2-year retrospective review was performed of all noncardiac, nonthoracic surgical patients that developed atrial fibrillation within 30 days of operation. Incidence, risk factors, treatment and outcome related to the development of this arrhythmia were analyzed. Fifty-one patients developed atrial fibrillation during this study period for an incidence of 0.37%. Most had preexisting cardiac risk factors, a positive fluid balance, or had electrolyte or arterial oxygen saturation abnormalities. Two thirds were discharged home on new cardiac medications, 16% remained in atrial fibrillation, and 12% died. New onset atrial fibrillation in this group of noncardiothoracic surgical patients is an uncommon problem that is a morbid event associated with significant mortality.


Foxi3GFP and Foxi3CreER mice allow identification and lineage labeling of pharyngeal arch ectoderm and endoderm, and tooth and hair placodes.
FOXI3 is a forkhead family transcription factor that is expressed in the progenitors of craniofacial placodes, epidermal placodes, and the ectoderm and endoderm of the pharyngeal arch region. Loss of Foxi3 in mice and pathogenic Foxi3 variants in dogs and humans cause a variety of craniofacial defects including absence of the inner ear, severe truncations of the jaw, loss or reduction in external and middle ear structures, and defects in teeth and hair. To allow for the identification, isolation, and lineage tracing of Foxi3-expressing cells in developing mice, we targeted the Foxi3 locus to create Foxi3GFP and Foxi3CreER mice. We show that Foxi3GFP mice faithfully recapitulate the expression pattern of Foxi3 mRNA at all ages examined, and Foxi3CreER mice can trace the derivatives of pharyngeal arch ectoderm and endoderm, the pharyngeal pouches and clefts that separate each arch, and the derivatives of hair and tooth placodes. Foxi3GFP and Foxi3CreER mice are new tools that will be of use in identifying and manipulating pharyngeal arch ectoderm and endoderm and hair and tooth placodes.


Selective Depletion of Antigen-Specific Antibodies for the Treatment of Demyelinating Disease.
Current treatments for antibody-mediated autoimmunity are associated with lack of specificity, leading to immunosuppressive effects. To overcome this limitation, we have developed a class of antibody-based therapeutics for the treatment of autoimmunity involving antibodies that recognize the autoantigen, myelin oligodendrocyte glycoprotein (MOG). These agents ("Seldegs," for selective degradation) selectively eliminate antigen (MOG)-specific antibodies without affecting the levels of antibodies of other specificities. Seldeg treatment of mice during antibody-mediated exacerbation of experimental autoimmune encephalomyelitis by patient-derived MOG-specific antibodies results in disease amelioration. Consistent with their therapeutic effects, Seldegs deliver their targeted antibodies to Kupffer and liver sinusoidal endothelial cells that are known to have tolerogenic effects. Our results show that Seldegs can ameliorate disease mediated by MOG-specific antibodies and indicate that this approach also has the potential to treat other autoimmune diseases where the specific clearance of antibodies is required.


Feasibility analysis of different surgical methods for uterine cesarean section scar diverticulum.
This study analyses the effects of surgical indicators and clinical efficacy of different surgical methods for uterine cesarean section scar diverticulum. This retrospective cohort study included 65 patients who underwent surgery and postoperative follow-up at Gansu Provincial Maternity and Child-care Hospital from 1 January 2013 to 31 February 2019. All participants were treated surgically. Among them, patients in Group A underwent combined laparoscopic and hysteroscopic surgery (n = 45), Group B underwent transvaginal surgery (n = 11), Group C underwent laparotomy (n = 9). The primary outcomes were surgical indicators. The secondary outcomes were clinical efficacy. Bleeding, operation time and hospitalization expenses were significantly different among the three groups (P < 0.05). There was no difference in the hospital stay among the three groups P = 0.22). The menstrual period before and after surgery was significantly different among the groups (P < 0.05). The recurrence outcome was no significantly different (P = 0.16), but the pregnancy outcome was not (P = 0.78). The three surgical methods are effective for treating cesarean section scar diverticulum with favorable effects. Laparoscopic combined with hysteroscopic surgery is minimally invasive with less bleeding compared with the other two techniques and it is easier for patients to accept. It is the most widely used surgical method.


Inflammatory-demyelinating polyneuropathies.
Recent advances in the pathogenesis and management of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are presented. These diseases are both diagnosable and treatable. The role of Campylobacter infection preceding GBS and the use of intravenous immunoglobulin to treat CIDP are discussed.


New population of odontoblasts responsible for tooth root formation.
Root formation is initiated with the extension of Hertwig's epithelial root sheath (HERS) after crown morphogenesis. To date, little is known about the molecular and cellular mechanisms controlling root formation. Recently we found rootless molars are formed in the dental mesenchyme-specific β-catenin conditional knockout mice. The striking root phenotypes of these mutant mice result from the disrupted differentiation of differentiating odontoblasts, caused by ablation of β-catenin during initiation of root formation. Here we show the cellular and molecular characteristics of differentiating odontoblasts using histochemistry and immunohistochemistry. These cells were not found in crown formation, but appeared only in the apical end of developing tooth, thus we have named these cells "apical odontoblasts" (AOds). AOds appeared immediately after HERS formation and were always present on the apical side of developing roots until root formation was complete. These findings indicate that AOds are closely associated with the transition from crown to root and with root elongation. In AOds, several transcription factors, including Nfic, Creb3l1, and Osx, as well as β-catenin and alkaline phosphatase were expressed but Phex and Dspp were not expressed. Taken together, our results indicate that AOds are the principal cells responsible for tooth root formation. These findings may contribute to the further understanding of the mechanisms underlying tooth root formation and root regeneration.


Electronic channel fringe holography for depth and delay measurements.
Electronic spectral holography in the form developed by Shih [Ph.D. dissertation, University Microfilms, Ann Arbor, Mich. (1995)] is adapted to various applications, including optical coherence tomography in scattering media, contouring of surfaces, and optical fiber mode examination.


Potts anastomosis in children with severe pulmonary arterial hypertension and atrial septal defect.
Potts shunt has been proposed as a bridge or alternative to lung transplantation for children with severe and drug-refractory suprasystemic pulmonary arterial hypertension (PAH). We describe the management of the atrial shunt when a Potts shunt is planned in refractory PAH. We report a case series of children in whom a Potts shunt was done for severe PAH associated with an atrial septal defect to illustrate the different clinical and haemodynamic scenarios. Five children (2 to 13 years) underwent a Potts shunt: three surgical, one percutaneous Potts shunt, and one percutaneous stenting of a restrictive arterial duct. All had associated atrial septal defect. Those who had generalized cyanosis before the procedure had a complicated postoperative course and required longer ventilatory and inotropic support, except the one who had atrial septal defect closure before the Potts shunt. One of the three cyanotic patients died. Two patients with left-to-right shunt before the Potts shunt had an uncomplicated postoperative course. Shunt physiology is only partially predictable after the Potts shunt in children with PAH and atrial septal defect. Abrupt drop in left ventricle preload while the right ventricle is decompressed can potentially be prevented by atrial septal defect closure prior to the Potts shunt.


The contents of visual memory are only partly under volitional control.
When we look around within a visual scene, is visual information automatically placed in visual memory during each saccade, or can we control which information is retained and which is excluded? We examined this question in five experiments by requiring participants to remember sequentially presented visual shapes or faces-some of which were marked for encoding (targets) and others that were supposed to be ignored (distractors)-over a 1-sec delay. The results show that distractors were retained in visual memory, regardless of stimulus category, suggesting that it is a general phenomenon. Whether or not participants were allowed to prepare for a target or distractor did not modulate distractor intrusion. When attention coupled with eye movements could be used to select targets, distractors were no longer encoded into memory. When eye movements were constrained, distractors once again intruded into memory. These findings suggest that top-down control processes are insufficient to filter the contents of visual memory.


Effects of anaesthesia using endotracheal intubation or the laryngeal mask airway, or spinal anaesthesia, on oral mucosal host defences during minor surgery.
Oral mucosal host defences are altered after anaesthesia and surgery. The effects of endotracheal intubation (ET) and the use of the laryngeal mask airway (LMA) on oral mucosal host defences after minor surgery were compared. Immunological (immunoglobulin A (IgA), IgG and IgM) and non-immunological (myeloperoxidase, total peroxidase, thiocyanate) oral host defence factors, and amylase and protein concentrations, were measured from saliva pre-operatively and on the first post-operative day in 60 ASA I-II patients undergoing minor surgery. The patients underwent general anaesthesia using oral ET or LMA. Spinal anaesthesia (S) was used as control. Serum IgG, IgM and IgA concentrations were determined. Protein-related salivary secretion of amylase and salivary concentration of IgM showed the only statistically significant overall differences between the groups. By contrast, changes were observed within the ET group in the salivary flow rate, protein concentration, amylase activity and immunological host defence factors. Some changes were also observed in the LMA group, but none in the S group. Most non-immunological test values did not change within any of the groups. ET and LMA induced similar oral mucosal host defence responses. There were, however, observations in this study that indicated a stronger response during ET than when LMA was used.


Coordinated tissue-specific regulation of adjacent alternative 3' splice sites in C. elegans.
Adjacent alternative 3' splice sites, those separated by ≤18 nucleotides, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron's 3' end depends upon sequence elements that define the branchpoint, polypyrimidine tract, and terminal AG dinucleotide. Starting with RNA-seq data from germline-enriched and somatic cell-enriched Caenorhabditis elegans samples, we identify hundreds of introns with adjacent alternative 3' splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is monodirectional, with somatic cells preferring to splice at the distal 3' splice site (furthest from the 5' end of the intron) and germline cells showing a distinct shift toward usage of the adjacent proximal 3' splice site (closer to the 5' end of the intron). Splicing patterns in somatic cells follow C. elegans consensus rules of 3' splice site definition; a short stretch of pyrimidines preceding an AG dinucleotide. Splicing in germline cells occurs at proximal 3' splice sites that lack a preceding polypyrimidine tract, and in three instances the germline-specific site lacks the AG dinucleotide. We provide evidence that use of germline-specific proximal 3' splice sites is conserved across Caenorhabditis species. We propose that there are differences between germline and somatic cells in the way that the basal splicing machinery functions to determine the intron terminus.


Dopachrome conversion factor functions as an isomerase.
Dopachrome conversion factor is an enzymatic activity associated with the pigmentary system which catalyzes the conversion of dopachrome, an intermediate in melanin biosynthesis, to dihydroxyindole-2-carboxylic acid (DHICA). To date, the mechanism of action of DCF has been unknown because all previous assays have employed a dopachrome substrate contaminated with L-dopa. It has therefore not been possible to determine whether L-dopa acts as a hydrogen donor in the reaction or whether the formation of DHICA occurs through an isomerization of dopachrome. In this study it is shown that DCF catalyzes the conversion of dopachrome to DHICA equally well in the presence or absence of L-dopa. The DCF-mediated reaction thus appears to be an isomeric rearrangement of hydrogen ions from one portion of the dopachrome molecule to another. The results indicate that the name "dopachrome isomerase" appropriately describes the function of DCF.


Coloradocin, an antibiotic from a new Actinoplanes. I. Taxonomy, fermentation and biological properties.
Coloradocin was discovered in a screen for anti-anaerobe activity. The producing organism was determined to be a new species of Actinoplanes, designated Actinoplanes coloradoensis sp. nov. Coloradocin inhibits Bacteroides, Clostridium and other anaerobes. It does not inhibit most aerobic bacteria but is effective against Neisseria gonorrhoeae and Haemophilus influenzae. Coloradocin has low acute toxicity.


Advances in radiation therapy for brain tumors.
Radiation therapy is used postoperatively as adjunctive therapy to decrease local failure; to delay tumor progression and prolong survival; as a curative treatment; as a therapy that halts further tumor growth; to alter function; and for palliation. Registration of MRI scan data sets with the treatment-planning CT scan is essential for accurate definition of the tumor and surrounding organs at risk. Integrating additional imaging studies that reflect the biologic characteristics of central nervous system tumors is an area of active research. Conformal treatment delivery is used to spare adjacent normal tissue from receiving unnecessary dose. In the dose range used when treating these tumors, the probability of causing serious late toxicity is relatively low and secondary malignancies are rare.


Catheter ablation of recipient right ventricular tachycardia after heterotopic heart transplantation.
Ventricular tachycardia after heart transplantation. A case is reported of ventricular tachycardia (VT) in a 62-year-old male after heterotopic heart transplantation, who occasionally had attacks of palpitation. Surface electrocardiogram suggested VT arising from the recipient heart. Intracardiac electrograms and entrainment mapping confirmed macroreentrant VT located in the recipient right ventricle. Radiofrequency ablation using an electroanatomical mapping system (CARTO, Biosense Webster, Diamond Bar, CA, USA) successfully eliminated VT.


Exposure to traumatic experiences among people addicted to alcohol.
The present studies point to high, i.e., approx. 70%, presence of at least one traumatic event over the life of people addicted to alcohol. The study involved 240 people - 120 people were addicted to alcohol (clinical group), including 60 women and 60 men, and 120 people were not addicted to alcohol (control group), including 60 women and 60 men. All people from the study group were asked to complete: The TAA-SR traumatic events assessment questionnaire, the structured interview checking the presence of experienced trauma and the severity of post-traumatic symptoms (PTSD) according to DSM-IV, and the personal survey. People addicted to alcohol experienced more traumas than non-addicted ones. The number of traumas of addicted women was significantly lower compared to addicted men. People addicted to alcohol reported the first experience of trauma much faster than non-addicted ones. The vast majority of people from the clinical group (addicted individuals) declared that the addiction symptoms occurred after experiencing the first trauma. The present studies point to high, i.e., approx. 70%, presence of at least one traumatic event over the life of people addicted to alcohol.


Mercurialism in the material of the Regional Centre of Acute Poisonings of the Institute of Rural Medicine in Lublin.
Against the background of clinical symptoms of mercury poisonings a case of suicidal poisoning which had favourable course and prognosis was presented. The impact of toxic renal damage and different CNS symptoms was emphasised.


Non-classical circulating monocytes expressing high levels of microsomal prostaglandin E2 synthase-1 tag an aberrant IFN-response in systemic sclerosis.
Systemic sclerosis (SSc) is a complex disease that affects the connective tissue, causing fibrosis. SSc patients show altered immune cell composition and activation in the peripheral blood (PB). PB monocytes (Mos) are recruited into tissues where they differentiate into macrophages, which are directly involved in fibrosis. To understand the role of CD14+ PB Mos in SSc, a single-cell transcriptome analysis (scRNA-seq) was conducted on 8 SSc patients and 8 controls. Using unsupervised clustering methods, CD14+ cells were assigned to 11 clusters, which added granularity to the known monocyte subsets: classical (cMos), intermediate (iMos) and non-classical Mos (ncMos) or type 2 dendritic cells. NcMos were significantly overrepresented in SSc patients and showed an active IFN-signature and increased expression levels of PTGES, in addition to monocyte motility and adhesion markers. We identified a SSc-related cluster of IRF7+ STAT1+ iMos with an aberrant IFN-response. Finally, a depletion of M2 polarised cMos in SSc was observed. Our results highlighted the potential of PB Mos as biomarkers for SSc and provided new possibilities for putative drug targets for modulating the innate immune response in SSc.


Human disease prediction from microbiome data by multiple feature fusion and deep learning.
Human disease prediction from microbiome data has broad implications in metagenomics. It is rare for the existing methods to consider abundance profiles from both known and unknown microbial organisms, or capture the taxonomic relationships among microbial taxa, leading to significant information loss. On the other hand, deep learning has shown unprecedented advantages in classification tasks for its feature-learning ability. However, it encounters the opposite situation in metagenome-based disease prediction since high-dimensional low-sample-size metagenomic datasets can lead to severe overfitting; and black-box model fails in providing biological explanations. To circumvent the related problems, we developed MetaDR, a comprehensive machine learning-based framework that integrates various information and deep learning to predict human diseases. Experimental results indicate that MetaDR achieves competitive prediction performance with a reduction in running time, and effectively discovers the informative features with biological insights.


Antibiotic utilization pattern in treatment of acute diarrheal diseases: the case of Hiwot Fana Specialized University Hospital, Harar, Ethiopia.
The vast majority of acute diarrheal diseases are self-limiting and do not require treatment on a regular basis. Empirical antibiotics should only be used to treat dysenteric and invasive bacterial diarrhea. Antibiotic misuse in the treatment of acute diarrhea is widespread in clinical practice worldwide. Hence, the purpose of this study was to examine the pattern of antibiotic use for the acute diarrheal diseases at Hiwot Fana Specialized University Hospital, Harar, Ethiopia. A retrospective, institution-based cross-sectional study was conducted to investigate the antibiotic utilization pattern for the treatment of acute diarrheal diseases from September 1 to September 30, 2022. Data were obtained retrospectively from patient cards treated for diarrheal disorders from August 1, 2021 to August 31, 2022, using standardized questionnaires, and the analysis was performed using IBM SPSS Statistics version 27. Among 332 patients in present study, 271 (81.63%) of them received nine different types of antibiotics, with the most commonly prescribed drugs were Cotrimoxazole (30.26%), Ciprofloxacin (19.19%), and Azithromycin (17.71%). Based on the presence of blood in the stools, 14.76% of the cases were invasive bacterial in nature. Antibiotics were prescribed about 2.55 times more frequently to patients under the age of 12 than to subjects 65 and older (AOR 2.55, 95% CI 1.45-3.87). Patients who received three or more medications were 2.77 times more likely to be prescribed antibiotics (AOR 2.77, 95% CI 1.84-7.56). For every unit increase in the number of drugs prescribed, the odds of prescribing antibiotics increased by 2.44 units (COR 2.44; 95% CI 2.06-4.32). The current study found that antibiotics were overused in both adults and children with acute diarrheal diseases at Hiwot Fana Specialized University Hospital. The number of antibiotics prescribed was significantly associated with the patient's age and the number of medications prescribed. To reduce antibiotic overuse, health professionals have to follow the national standard treatment guidelines.


Fourteen years of gastric tubes.
Since 1964 gastric tube replacement of the esophagus has been done in 30 infants and children. This report reviews and brings up to date our entire series, which includes follow-up of 15 children over 5 yr, 7 of whom have been followed for more than 10 yr. The two-stage proximally based reversed antiperistaltic gastric tube placed retrosternally is still our procedure of choice, although since our last report in 1973 several other methods (one-stage, transthoracic, subcutaneous) have been used, and the spleen has not been removed in our more recent operations. Whether the esophagogastric tube anastomosis is primary or secondary or is in the chest or neck, leakage is still the most common complication (63%), with all but three closing spontenously. A continuing problem may be an anastomotic stricture (43%) that will require some dilatations. Mild sacculation or tortuosity of the gastric tube has been encountered only once. Despite the above problems, the eventual outcome in the growing child with a gastric tube replacement continues to be a satsifying one. We continue to use the gastric tube operation when replacement of the esophagus is required.


Prevalence of breastfeeding in a baby-friendly pediatric practice: an experience in Trieste, Italy.
In a pediatric practice in Italy, actions were undertaken to apply the recommendations for a breastfeeding-friendly physician's office and to promote the adoption of a semi-reclined or laid-back maternal position in breastfeeding. The aim of this study is to evaluate the effect of the actions implemented, in terms of prevalence of exclusive breastfeeding. A historical cohort study was carried out using administrative data routinely collected. All women who gave birth in 2016 and registered their newborns with the pediatric practice were included, only mothers of preterm newborns < 30 weeks gestational age were excluded. The main actions undertaken were: employment of a breastfeeding peer supporter; ensuring unlimited daily access in case of breastfeeding difficulties; provision of individual support to breastfeeding mothers in a dedicated room and advice on the laid-back position; scheduling of weekly meetings of small groups for breastfeeding support. Each infant was followed up for five months. The main study outcomes were duration of exclusive breastfeeding (only breast milk and no other liquids or solids, except for drops of syrups with nutritional supplements or medicines) and prevalence at five months. A total of 265 newborn infants with a gestational age greater than 30 weeks were registered with the pediatric practice during the study period, about 18% of all infants born in Trieste in that period. Complete data were available for 252 of these (95.1%). The rate of exclusive breastfeeding at five months of age was higher than the one reported for the whole infant population of Trieste and of the Friuli Venezia Giulia Region (62.3% vs. 42.9% vs. 30.3%) in the same period. The implementation of breastfeeding-friendly pediatric practice and the application of laid-back breastfeeding may improve the rate and duration of exclusive breastfeeding.


Allergy to Surgical Implants.
Surgical implants have a wide array of therapeutic uses, most commonly in joint replacements, but also in repair of pes excavatum and spinal disorders, in cardiac devices (stents, patches, pacers, valves), in gynecological implants, and in dentistry. Many of the metals used are immunologically active, as are the methacrylates and epoxies used in conjunction with several of these devices. Allergic responses to surgical components can present atypically as failure of the device, with nonspecific symptoms of localized pain, swelling, warmth, loosening, instability, itching, or burning; localized rash is infrequent. Identification of the specific metal and cement components used in a particular implant can be difficult, but is crucial to guide testing and interpretation of results. Nickel, cobalt, and chromium remain the most common metals implicated in implant failure due to metal sensitization; methacrylate-based cements are also important contributors. This review will provide a guide on how to assess and interpret the clinical history, identify the components used in surgery, test for sensitization, and provide advice on possible solutions. Data on the pathways of metal-induced immune stimulation are included. In this setting, the allergist, the dermatologist, or both have the potential to significantly improve surgical outcomes and patient care.


Cost and effectiveness of laser with phlebectomies compared with foam sclerotherapy in superficial venous insufficiency. Early results of a randomised controlled trial.
Quantify endovenous laser ablation (EVLA) with concurrent phlebectomies and ultrasound-guided foam sclerotherapy (UGFS) in cost and effectiveness at 3 weeks and 3 months. Single-centre, prospective, randomised controlled trial. One hundred patients (100 legs), C(2-6), age 21-78, M:F 42:58, with primary varicose veins received either EVLA under local anaesthetic or UGFS. Assessments included duplex, Aberdeen varicose vein questionnaire (AVVQ), venous clinical severity score (VCSS), venous filling index (VFI), visual analogue 7-day pain score and analgesia requirements. Additional treatments with UGFS were performed, if required. Micro-costing, using individually timed treatments, was based on consumables, staff pay and overheads. Changes in AVVQ, VCSS and VFI values (3 months) did not demonstrate any significant difference between groups. At 3 months, the above-knee GSV occlusion rate (without co-existing reflux) was not significantly different between the groups (74% vs 69%; EVLA vs UGFS; P = .596). Of the 9 haemodynamic failures in each group, 7 EVLA patients and 4 UGFS patients had co-existing cross-sectional above-knee GSV occlusion at some point. However, UGFS significantly outperformed EVLA in cost, treatment duration, pain, analgesia requirements and recovery. UGFS is 3.15 times less expensive than EVLA (£230.24 vs £724.72) with comparable effectiveness but 56% (versus 6%) required additional foam (ISRCTN:03080206).


Describing the trend of ammonia, particulate matter and nitrogen oxides: The role of livestock activities in northern Italy during Covid-19 quarantine.
Nitrogen oxides (NOx), sulphur oxides (SOx) and ammonia (NH3) are among the main contributors to the formation of secondary particulate matter (PM2.5), which represent a severe risk to human health. Even if important improvements have been achieved worldwide, traffic, industrial activities, and the energy sector are mostly responsible for NOx and SOx release; instead, the agricultural sector is mainly responsible for NH3 emissions. Due to the emergency of coronavirus disease, in Italy schools and universities have been locked down from late February 2020, followed in March by almost all production and industrial activities as well as road transport, except for the agricultural ones. This study aims to analyze NH3, PM2.5 and NOx emissions in principal livestock provinces in the Lombardy region (Brescia, Cremona, Lodi, and Mantua) to evaluate if and how air emissions have changed during this quarantine period respect to 2016-2019. For each province, meteorological and air quality data were collected from the database of the Regional Agency for the Protection of the Environment, considering both data stations located in the city and the countryside. In the 2020 selected period, PM2.5 reduction was higher compared to the previous years, especially in February and March. Respect to February, PM2.5 released in March in the city stations reduced by 19%-32% in 2016-2019 and by 21%-41% in 2020. Similarly, NOx data of 2020 were lower than in the 2016-2019 period (reduction in March respect to February of 22-42% for 2016-2019 and of 43-62% for 2020); in particular, this can be observed in city stations, because of the current reduction in anthropogenic emissions related to traffic and industrial activities. A different trend with no reductions was observed for NH3 emissions, as agricultural activities have not stopped during the lockdown. Air quality is affected by many variables, for which making conclusions requires a holistic perspective. Therefore, all sectors must play a role to contribute to the reduction of harmful pollutants.


Spatial and temporal variability in macroalgal blooms in a eutrophied coastal estuary.
All three macroalgal clades (Chlorophyta, Rhodophyta, and Phaeophyceae) contain bloom-forming species. Macroalgal blooms occur worldwide and have negative consequences for coastal habitats and economies. Narragansett Bay (NB), Rhode Island, USA, is a medium sized estuary that is heavily influenced by anthropogenic activities and has been plagued by macroalgal blooms for over a century. Over the past decade, significant investment has upgraded wastewater treatment from secondary treatment to water-quality based limits (i.e. tertiary treatment) in an effort to control coastal eutrophication in this system. The goal of this study was to improve the understanding of multi-year macroalgal bloom dynamics through intensive aerial and ground surveys conducted monthly to bi-monthly during low tides in May-October 2006-2013 in NB. Aerial surveys provided a rapid characterization of macroalgal densities across a large area, while ground surveys provided high resolution measurements of macroalgal identity, percent cover, and biomass. Macroalgal blooms in NB are dominated by Ulva and Gracilaria spp. regardless of year or month, although all three clades of macroalgae were documented. Chlorophyta cover and nutrient concentrations were highest in the middle and upper bay. Rhodophyta cover was highest in the middle and lower bay, while drifting Phaeophyceae cover was patchy. Macroalgal blooms of >1000g fresh mass (gfm)/m2 (max=3510gfm/m2) in the intertidal zone and >3000gfm/m3 (max=8555gfm/m3) in the subtidal zone were observed within a heavily impacted embayment (Greenwich Bay). Macroalgal percent cover (intertidal), biomass (subtidal), and diversity varied significantly between year, month-group, site, and even within sites, with the highest species diversity at sites outside of Greenwich Bay. Total intertidal macroalgal percent cover, as well as subtidal Ulva biomass, were positively correlated with temperature. Dissolved inorganic nitrogen concentrations were correlated with the total biomass of macroalgae and the subtidal biomass of Gracilaria spp. but not the biomass of Ulva spp. Despite seasonal reductions in the nutrient output of wastewater treatment facilities emptying into upper Narragansett Bay in recent years, macroalgal blooms still persist. Continued long-term monitoring of water quality, macroalgal blooms, and ecological indicators is essential to understand the changes in macroalgal bloom dynamics that occur after nutrient reductions from management efforts.


Changes in structural organization of surface membrane during erythrocyte maturation.
The effect of concanavalin A and its succinylated derivative on cell agglutination and potassium compartmentation of mature and immature erythrocytes was observed. The binding of tetravalent concanavalin A to the surface glycoproteins of rabbit erythrocytes leads to a change in the properties of the surface membrane, which results in an induction of cell agglutination and concomitant release of potassium from the cells. Both of the phenomena induced by concanavalin A are temperature dependent, and observed at above 15 degrees C. Divalent succinylated concanavalin A, lacking the inducing activity of surface glycoprotein cross-linking into patches and caps, caused neither cell agglutination nor change in the potassium compartmentation of erythrocytes and reticulocytes. In the case of immature reticulocytes, however, remarkable agglutination of the cells was induced without a change in the potassium compartmentation after treatment with tetravalent concanavalin A. It is suggested that changes in the molecular organization of the surface membrane occur in which potassium compartmentation of the reticulocytes becomes more susceptible to surface glycoprotein cross-linking during cellular maturation.


Do bladder neck mobility and urethral sphincter function differ during pregnancy compared with during the non-pregnant state?
The aim of the study was to assess and compare urethral sphincter (US) function and bladder neck (BN) behavior in pregnant and non-pregnant women. Urethral pressure profile parameters, intravaginal-anal pressures and BN position/mobility were compared in both pregnant and non-pregnant women. It was found that pregnancy results in a decreased maximal urethral closure pressure (MUCP)/area of continence at rest and at stress, decreased pressure-transmission ratio (PTR) values and backwards displacement of the bladder neck. No significant changes in intravaginal-anal pressures and BN mobility/downwards displacement were seen. Compared with stress continent pregnant patients, pregnant patients with stress urinary incontinence (SUI) have a lower MUCP at rest/stress and area of continence at stress, but show no difference in BN behavior. Regression analysis shows no correlation between advancing pregnancy and any of these parameters. It was concluded that pregnancy induces diminished US function and backwards displacement of the BN. Compared to continent pregnant patients, pregnant women with SUI also have a diminished US function. US parameters are not significantly modified by advancing pregnancy.


Early intervention in psychosis: service models worldwide and the Irish experience.
This paper examines the concept of early intervention in psychosis at primary and secondary prevention levels. Examples of early intervention service models from different countries are presented and we discuss current evidence for efficacy. We highlight the Irish experience of early intervention to date, and discuss future implementation of early intervention services in Ireland.


Possible neurophysiological markers of early neurodegenerative process: Parkinson's disease.
We used tests for evaluation of latent period, duration, and accuracy of eyes, head, or hand movements and their coordinated movements. Comparative analysis of these parameters was performed in healthy subjects and in patients with early stages of Parkinson's disease. The pathology data significantly (p<0.05) differed from those in normal control subjects. These results can be used as neurophysiological markers of early neurodegenerative process. Increasing the number of tests would lead to better specificity of the markers. It will be possible to create a battery of neurophysiological tests most likely reflecting the predictive basis of early neurodegenerative process.


Microcirculatory dysfunction in cardiogenic shock.
Cardiogenic shock is usually defined as primary cardiac dysfunction with low cardiac output leading to critical organ hypoperfusion, and tissue hypoxia, resulting in high mortality rate between 40% and 50% despite recent advances. Many studies have now evidenced that cardiogenic shock not only involves systemic macrocirculation, such as blood pressure, left ventricular ejection fraction, or cardiac output, but also involves significant systemic microcirculatory abnormalities which seem strongly associated with the outcome. Although microcirculation has been widely studied in the context of septic shock showing heterogeneous alterations with clear evidence of macro and microcirculation uncoupling, there is now a growing body of literature focusing on cardiogenic shock states. Even if there is currently no consensus regarding the treatment of microcirculatory disturbances in cardiogenic shock, some treatments seem to show a benefit. Furthermore, a better understanding of the underlying pathophysiology may provide hypotheses for future studies aiming to improve cardiogenic shock prognosis.


A retrospective observational study of antimicrobial treatment for non-tuberculous mycobacteria disease using a nationwide claims database in Japan.
The Macrolides (MLs), clarithromycin and azithromycin, are key drugs for non-tuberculous mycobacteria (NTM) diseases treatment. A three antibiotics regimen including MLs, rifampicin (RFP) and ethambutol (EB) has been recommended for the treatment of NTM diseases in ATS/IDSA guideline. However, anti-biotics are not necessarily prescribed in compliance with the guideline. Inappropriate regimens are risk of introducing MLs resistance. Therefore, we planned this study to evaluate the current Japanese NTM diseases treatment conditions. We used the national database (NDB) from 2011 to 2014. A total of 183 patients were entered into the study. The patients number increased at an accelerating rate in patients aged ≥55 years. Patients aged ≥55 years made up 91.3% of the total NTM diseases. Male and female patients were 61 and 122, respectively, a female/male ratio of 2.00. Clarithromycin, RFP, EB and fluoroquinolones were frequently prescribed, with the numbers of prescriptions being 125, 66, 57 and 45, respectively. The regimen of MLs, RFP and EB recommend by ATS/IDSA guideline 2007 was only followed by 25.1% of the patients. MLs monotherapy was as high as 30.6% of NTM diseases and would be a risk factor leading to an increase of MLs resistance and poor treatment outcome. Without effective NTM disease therapy, the increase of MLs-resistant NTM diseases would be a burden for Japanese health care facilities.


Variable regions in the sushi domains 6-7 and 19-20 of factor H in animals and human lead to change in the affinity to factor H binding protein of Borrelia.
Borrelia binds host's complement regulatory factor H (fH) to evade complement attack. However, binding affinities between fH-binding-proteins (FHBPs) of Borrelia and fH from various hosts are disparate. Experiments performed to unfold the underlying molecular basis of this disparity revealed that recombinant BbCRASP-1 (major FHBP of Borrelia burgdorferi) neither interacted with sushi 6-7, nor with sushi 19-20 domains of fH in cattle and pig, however, showed binding affinity to both sushi domains of human fH, sushi 6-7 of mouse and sushi 19-20 of sheep. Further, peptide-spot assay revealed three major binding sites (sushi 6:(335-346), sushi 7:(399-410) and sushi 20:(1205-1227)) in human fH that can form BbCRASP-1:fH interface, while (337)HENMR(341) residues in sushi 6 are crucial for rigid BbCRASP-1:fH complex formation. Amino acid stretches DTIEFTCRYGYRPRTALHTFRTT in ovine sushi 19-20 and SAYWEKVYVQGQ in mouse sushi 7 were important sites for fH:BbCRASP-1 interaction. Comparative analysis of the amino acid sequences of sushi 6 of cattle, pig and human revealed that bovine and porcine fH lack methionine and arginine in HENMR pocket, that may impede formation of fH:BbCRASP-1 interface. Increasing numbers of FHBPs from animal and human pathogens are being discovered, thus results presented here can be important benchmark for study of other FHBPs:FH interactions.


Inherited persistence of immature type pyruvate kinase and hexokinase isozymes in dog erythrocytes.
1. Red cell pyruvate kinase (EC 220.127.116.11) and hexokinase (EC 18.104.22.168) in high and low potassium (K) dogs were shown to exist as multiple forms which were separable by electrophoresis and ion-exchange chromatography. The R2-type pyruvate kinase, which was determined to be a young type enzyme in canine red cells, was shown to be the predominant form of pyruvate kinase in high K cells. 2. The M2-type pyruvate kinase, a prototype isozyme in erythroid cells, existed in high K dog erythrocytes as well as in high K and low K dog reticulocytes. 3. Isozyme analysis of high K red cell hexokinase also showed a profile similar to that obtained for low K reticulocytes. 4. These results seem to reflect the immaturity of high K erythrocytes, which suggest that an abnormal cell differentiation or maturation may occur at an early stage of erythroid cell proliferation in high K dogs.


Autism in Preschool-Aged Children: The Effects of COVID-19 Lockdown.
The COVID-19 lockdown affected children, especially those with autism spectrum disorder, due to the disruption in rehabilitation and educational activities. We conducted a cross-sectional study of 315 preschool-aged children, 35 of which had autism, to investigate this impact. A questionnaire was administered to explore socio-demographic status, familiar/home environment, and COVID-19 exposure. The clinical features of autistic subjects were also examined. Seven variables were considered to describe the effect of pandemic: Remote learning, Behavior changes, Home activities, Sleep habits, Night awakenings, Physical activity, Information about the virus. The lockdown had a significant impact on Remote learning, Behavior changes, and Information about the virus in participants with autism. Moreover, we found a worsening in repetitive movements, echolalia, restricted interests, and aggressive behaviors.


Seroepidemiological survey of rickettsial infections among blood donors in central Tunisia.
In this report we attempt to evaluate the prevalence of antibodies against Rickettsia conorii, R. typhi, Coxiella burnettii, and Ehrlichia chaffeensis in central Tunisia. Five hundred sera from blood donors, collected between March and June 1993, were tested for these 4 antibodies using an indirect immunofluorescence antibody assay (IFA). Nine percent of the sera had antibodies against R. conorii (IgG > 1:32) by IFA, and 8% by Western blotting; with IFA, 3.6% had antibodies to R. typhi, 26% to C. burnetii (> 1:50), and none to E. chaffeensis. Infection rates with R. conorii and R. typhi did not differ significantly between the sexes, but fewer young people had antibodies to R. typhi. A significantly higher prevalence of antibodies to C. burnetii was noted for males with no difference between age classes. No significant difference was detected between urban and rural areas. This study confirmed the endemicity of rickettsioses, and revealed a high seroprevalence of Q fever, in central Tunisia.


Low back pain recollection versus concurrent accounts: outcomes analysis.
Patients with low back pain were asked to recall the pain and impaired functioning that they reported 5-10 years previously as part of the National Low Back Pain prospective follow-up study. In 1998, patients completed an additional follow-up. To compare outcomes using patient-recalled data and prospectively collected data from patients with low back pain and to identify simple, symptom-specific questions that yield reliable responses over an extended period of time. Outcome assessment based on patient recall may be influenced by a patient's age, gender, reporting tendency, and current health status. The impact of data collected retrospectively on outcome analyses in spinal patients has not been addressed. Patients enrolled in the National Low Back Pain study from 1986 to 1991 completed a self-administered questionnaire at their initial visit. A sample was interviewed by telephone in 1996 and asked to recall pain characteristics and impaired functioning reported at initial examination. A 10-year follow-up (1998) on current health status was conducted by mail. The 1998 follow-up response was separately compared with recalled and initial responses, such that two patient outcome status values were calculated for each question. Agreement was evaluated using Cohen's kappa. The follow-up evaluation was completed by 144 patients, with a mean interval of 9.4 years. The overall simple kappa was 0.37, indicating "fair" agreement between outcomes based on initial and recalled accounts of pain. Questions on location of pain had kappa values of 0.12-0.58, radicular symptoms 0.28-0.48, and severity of pain 0.11-0.30. "Fair" to "moderate" agreement was found between outcomes determined by recalled versus initial reports. Accuracy was greatest for queries on frequency, location of pain, and activities affecting pain. Discrepancies were noted for queries on severity of pain, with error bias toward less pain when using the recalled data. Careful selection of questions may yield more accurate outcome measures.


Effects of clipping and soil compaction on growth, morphology and mycorrhizal colonization of Schizachyrium scoparium, a C4 bunchgrass.
A factorial design of clipping and compaction was used to study the responses of Schizachyrium scoparium and its mycorrhizal symbionts to these stresses. All treatment combinations significantly reduced the growth and biomass of plants relative to controls. Compaction significantly reduced tillering and crown expansion while clipping increased tillering early in the growing season and reduced it later. Mycorrhizal colonization of roots was highest in the clipped plots and lowest in compacted plots. Spore number was highest in compacted plots and lowest in clipped plots. It appears that spore number may be negatively correlated with root growth since any treatment that reduced plant growth yielded higher spore numbers. The combination of clipping and compaction reduced plant growth the most, but had intermediate effects on mycorrhizal colonization and spore number.


Microwave-assisted extraction in natural products isolation.
Microwave-assisted extraction (MAE) or simply microwave extraction is a relatively new extraction technique that combines microwave and traditional solvent extraction. Application of microwaves for heating the solvents and plant tissues in extraction process, which increases the kinetic of extraction, is called microwave-assisted extraction. MAE has a number of advantages, e.g., shorter extraction time, less solvent, higher extraction rate and lower cost, over traditional method of extraction of compounds from various matrices, especially natural products. The use of MAE in natural products extraction started in the late 1980s, and through the technological developments, it has now become one of the popular and cost-effective extraction methods available today, and several advanced MAE instrumentations and methodologies have become available, e.g., pressurized microwave-assisted extraction (PMAE) and solvent-free microwave-assisted extraction (SFMAE). This chapter provides an overview of the MAE and presents a number of specific protocols for natural products extraction.


Electrochemical and spectro-kinetic evidence for an intermediate electron acceptor in photosystem I.
Absorption changes accompanying light-induced P-700 formation and its decay in the dark at 15 K in Photosystem-I particles poised at various redox potentials have been examined. In unpoised samples, the light-induced absorption change is practically irreversible. At increasingly negative potentials, an increasing fraction of the absorption change, proportional to the fraction of bound iron-sulfur protein chemically reduced, becomes reversible, and the titration curve has a midpoint potential of --530 mV (vs. normal hydrogen electrode). At --66 mV, the P-700 absorption change is 97% reversible. The total P-700-signal amplitude decreases over the same potential span and levels off at about 43% (to slightly over 50% at a substantially higher excitation intensity). These results provide additional support to previous suggestions of an existence of an intermediate electron acceptor located between the primary donor, P-700, and the more stable primary electron acceptor (P-430 or bound iron-sulfur protein).


[Nature of the correlation of the adrenergic reactions of the heart and coronary vessels in coronary circulatory disorder].
In acute experiments on dogs it was shown that under the conditions of a moderate (by 30 and 50%) decrease of the coronary blood flow, a quantitative and qualitative dissociations of changes in adrenergic reactions of the heart and coronary vessels to isadrin and noradrenaline occur--this was manifested by a distinct suppression of dilatational coronary reactions with a less pronounced suppression or even enhancement of adrenergic effects of the heart.


The effects of neonatal androgenization on the in vivo transport of alpha-aminoisobutyric acid into specific regions of the rat brain.
The purpose of the present study was to determine if the administration of testosterone propionate (TP) to neonatal rats is followed in vivo by alterations in the transport of the non-metabolizable amino acid, alpha-aminoisobutyric acid (AIB), into specific regions of the brain. Forty-eigh hours after birth, male and female rats were injected s.c. with either 1,25 mg TP or an equivalent volume of vehicle. Five, 10 and 17 days after birth, control and TP-treated rats were decapitated at intervals of 2, 5, 60 and 300 min after the i.p. injection of 0.25 muCi [1-14C]alpha-aminoisobutyric acid/g body weight. Twelve brain regions, i.e., amygdala, cerebellum, corpora quadrigemina, frontal cortex, hypothalamus, medulla, occipital cortex, olfactory bulbs, olfactory tubercles, parietal cortex, pons, pyriform cortex and samples of serum were analyzed in terms of disint./min/mg tissue and as tissue/serum (T/S) ratios. At the end of 300 min there was a significant increase in the active transport of AIB in all brain regions of the 5-days-old TP-treated rats. Similarly, by 300 min, the active transport of AIB was significantly increased in all brain regions sxcept cerebellum and pons of the 10-day-old TP-treated rats. The administration of TP to neonatal rats did not alter the accumulation and/or active transport of AIB in brain regions of the 17-day-old rat at any of the tested intervals. These data indicate that (1) neonatally administered TP enhanced (either directly or indirectly) the transport and/or accumuation of AIB in specific brain regions of 5- and 10-day-old rats and (2) the effectiveness of the steroid decreased with the age of the rat.


Enhanced thyroxine removal from micro-polluted drinking water resources in a bio-electrochemical reactor amended with TiO2@GAC particles: Efficiency, mechanism and energy consumption.
A three-dimensional bioelectrochemical system (3D-BES) with both electrocatalytic and biodegradation functions was designed and developed to enhance iodine-containing hormone removal from micro-polluted oligotrophic drinking water sources and to reduce energy consumption. Thyroxine (T4) removal efficiency was 99.0% in the 3D-BES amendment with TiO2@GAC as the particle electrodes, which was 20.5% higher than the total efficiency of single biodegradation (28.7%) plus electrochemical decomposition (49.8%). The high T4 removal efficiency was a result of biochemical synergistic degradation, enhancement of electron transfer and utilization, enrichment of functional microorganisms, and the expression of dehalogenation functional genes. The electron transfer was increased by 1.63 times in 3D-BES compared to the 2D-BES, which contributed to: (i) ∼17.8% enhancement of dehalogenation, (ii) 2.35 times enhancement of the attenuation rate, and (iii) 60% reduction in energy consumption. Moreover, the aggregation of microorganisms and the hydrophobic T4 onto TiO2@GAC shortened the transfer distance of matter and energy, which induced the degradation steps to be shortened and the toxic decay to be accelerated from T4 and its metabolites. These comprehensive functions also enhanced the 31.8% ATPase activity, 7.3% abundance of the functional reductive dehalogenation genera, and 52.3% dehalogenation genes expression for Pseudomonas, Ancylobacter, and Dehalogenimonas, which contributed to an increase in T4 removal. This work provides an environmental-friendly biochemical synergistic method for the detoxification of T4 polluted water.


Acute pain management in dermatology: mechanisms and pathways.
The number of dermatologic surgical procedures performed is increasing each year. The pain associated with these procedures is a major concern for patients and its treatment is part of the increasing emphasis on outcomes and quality of clinical care. Better understanding of pain signaling and how commonly used analgesics function can help improve our surgical pain management. This is part I of a 2-part review that will highlight the anatomy of acute pain signaling from the skin to the central nervous system and the factors that influence the plasticity of the pathway. Having this foundation of knowledge is needed to enhance the clinical treatment of pain. Part II will provide an updated review of available treatments, with an emphasis on their appropriate use for postsurgical pain management.


Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis.
Genome damage and defective repair are etiologically linked to neurodegeneration. However, the specific mechanisms involved remain enigmatic. Here, we identify defects in DNA nick ligation and oxidative damage repair in a subset of amyotrophic lateral sclerosis (ALS) patients. These defects are caused by mutations in the RNA/DNA-binding protein FUS. In healthy neurons, FUS protects the genome by facilitating PARP1-dependent recruitment of XRCC1/DNA Ligase IIIα (LigIII) to oxidized genome sites and activating LigIII via direct interaction. We discover that loss of nuclear FUS caused DNA nick ligation defects in motor neurons due to reduced recruitment of XRCC1/LigIII to DNA strand breaks. Moreover, DNA ligation defects in ALS patient-derived iPSC lines carrying FUS mutations and in motor neurons generated therefrom are rescued by CRISPR/Cas9-mediated correction of mutation. Our findings uncovered a pathway of defective DNA ligation in FUS-linked ALS and suggest that LigIII-targeted therapies may prevent or slow down disease progression.


Epidemiology and significance of Q fever in Czechoslovakia.
Over the last 35 years most parts of Czechoslovakia have experienced Q fever. Of particular note were outbreaks in factories processing imported cotton, wool and hides that had been contaminated in their countries of origin. Some areas of the southern part of Central Slovakia became a natural focus of Q fever with the Dermacentor marginatus tick being the main vector of coxiellae. Currently, Coxiella (C.) burnetii infection appears to be dormant in the country since only sporadic cases are encountered. Cattle vaccination practiced since 1980 may have contributed to the decreasing incidence of human Q fever.


A simple method for the automatic classification of body parts and detection of implanted metal using postmortem computed tomography scout view.
Information on medical devices embedded in the body is important in the identification of an unidentified body. Computed tomography (CT) is a powerful imaging modality; however, metallic artifacts deteriorate the image quality because of the reconstruction method. On the contrary, CT scout view is less affected by metallic artifacts compared to CT. It is a simple method to classify the body into three rough parts for postmortem CT (PMCT) scout view, and an algorithm used to detect the location of the implanted metal has been developed for personal identification in forensic pathology. Of the test images, 97% were correctly classified into the three body parts. The true-positive rate for detection of the implanted metal in the scout view was 96.5%. Therefore, our simple methods are applicable in PMCT scout views and would be particularly useful for forensic pathology.