Recent developments in ultrasound approach for preservation of animal origin foods.
Ultrasound is a contemporary non-thermal technology that is currently being extensively evaluated for its potential to preserve highly perishable foods, while also contributing positively to the economy and environment. There has been a rise in the demand for food products that have undergone minimal processing or have been subjected to non-thermal techniques. Livestock-derived food products, such as meat, milk, eggs, and seafood, are widely recognized for their high nutritional value. These products are notably rich in proteins and quality fats, rendering them particularly vulnerable to oxidative and microbial spoilage. Ultrasound has exhibited significant antimicrobial properties, as well as the ability to deactivate enzymes and enhance mass transfer. The present review centers on the production and classification of ultrasound, as well as its recent implementation in the context of livestock-derived food products. The commercial applications, advantages, and limitations of the subject matter are also subject to scrutiny. The review indicated that ultrasound technology can be effectively utilized in food products derived from livestock, leading to favorable outcomes in terms of prolonging the shelf life of food while preserving its nutritional, functional, and sensory attributes. It is recommended that additional research be conducted to investigate the effects of ultrasound processing on nutrient bioavailability and extraction. The implementation of hurdle technology can effectively identify and mitigate the lower inactivation of certain microorganisms or vegetative cells.


Phosphatidylinositol 4,5-biphosphate (PIP2) modulates interaction of syntaxin-1A with sulfonylurea receptor 1 to regulate pancreatic β-cell ATP-sensitive potassium channels.
In β-cells, syntaxin (Syn)-1A interacts with SUR1 to inhibit ATP-sensitive potassium channels (KATP channels). PIP2 binds the Kir6.2 subunit to open KATP channels. PIP2 also modifies Syn-1A clustering in plasma membrane (PM) that may alter Syn-1A actions on PM proteins like SUR1. Here, we assessed whether the actions of PIP2 on activating KATP channels is contributed by sequestering Syn-1A from binding SUR1. In vitro binding showed that PIP2 dose-dependently disrupted Syn-1A·SUR1 complexes, corroborated by an in vivo Forster resonance energy transfer assay showing disruption of SUR1(-EGFP)/Syn-1A(-mCherry) interaction along with increased Syn-1A cluster formation. Electrophysiological studies of rat β-cells, INS-1, and SUR1/Kir6.2-expressing HEK293 cells showed that PIP2 dose-dependent activation of KATP currents was uniformly reduced by Syn-1A. To unequivocally distinguish between PIP2 actions on Syn-1A and Kir6.2, we employed several strategies. First, we showed that PIP2-insensitive Syn-1A-5RK/A mutant complex with SUR1 could not be disrupted by PIP2, consequently reducing PIP2 activation of KATP channels. Next, Syn-1A·SUR1 complex modulation of KATP channels could be observed at a physiologically low PIP2 concentration that did not disrupt the Syn-1A·SUR1 complex, compared with higher PIP2 concentrations acting directly on Kir6.2. These effects were specific to PIP2 and not observed with physiologic concentrations of other phospholipids. Finally, depleting endogenous PIP2 with polyphosphoinositide phosphatase synaptojanin-1, known to disperse Syn-1A clusters, freed Syn-1A from Syn-1A clusters to bind SUR1, causing inhibition of KATP channels that could no longer be further inhibited by exogenous Syn-1A. These results taken together indicate that PIP2 affects islet β-cell KATP channels not only by its actions on Kir6.2 but also by sequestering Syn-1A to modulate Syn-1A availability and its interactions with SUR1 on PM.


Evaluation of buccal methyl-beta-cyclodextrin toxicity on human oral epithelial cell culture model.
Cyclodextrins, especially methylated beta-cyclodextrins offer several advantages for drug delivery which include improved drug solubilization, protection against physicochemical and enzymatic degradation, as well as a potential for absorption improvement. However, little or no data are available for their use as drug penetration enhancer via the buccal route. This study focuses on the toxicity of randomly methylated beta-cyclodextrin (RAMEB) on buccal mucosa using a reconstituted human oral epithelium model composed of TR 146 cells. Toxicity of RAMEB on TR 146 cells was evaluated by measuring cell viability (MTT assay) and membrane damages followed by LDH release after single and repeated exposures to RAMEB solutions. Inflammatory effects of RAMEB are also considered by measuring expression of interleukin-1alpha and are supported by histological examination. The present results indicate that 10% RAMEB results in cytotoxic and inflammatory effects depending on time exposure, whereas 2% and 5% RAMEB do not induce tissue damages even after 5 days of repeated exposures. Therefore, the highly water-soluble RAMEB is thought to be a safe candidate as an excipient for buccal mucosal drug delivery.


[Undergraduate on Public Health: limits and possibilities as a professional education strategy].
This article aims to call into question Public Health as a field for professionalization by systematizing theoretical, social and ethical-political bases for undergraduate education. We also attempt to record the trajectory in formulating undergraduate courses in that field and, more recently, the emergence of these projects in Brazilian Universities. In Brazil, the current projects are a result of institutional experience gained in Public Health teaching in different undergraduate courses in the field of health. Additionally, there is also a teaching tradition in non-degree and master's and PhD graduate courses. International experiences from similar courses, as well as orientation from international agencies represent important information for such initiatives. Furthermore, policies targeting social inclusion and the expansion in the number of student places in higher education have been propelling the movement. There is also the realization that the Brazilian Public Health System demands new actors able to provide answers which are both different and complementary to those offered by traditional undergraduate courses. While several institutions are in the stage of offering this education to society, this article presents a set of elements which are derived from reflection in the epistemological, sociological and political-sanitary spheres.


[The clinical effectiveness of a post milking teat disinfection method with a foaming iodophor teat dip].
The effect of postmilking teat dipping with a foaming iodophor agent on incidence of intramammary infections (IMI), incidence of clinical mastitis, somatic cell count and the characteristics of udder tissue and teat was investigated in a positively controlled field study. Two groups of animals were compared. Teats were dipped with a foaming iodophor in the treatment group (TG, 122 animals) while teats in the control group (CG, 121 animals) were dipped with a conventional iodophor teat dip with the same iodine content. A bacteriological examination of quarter milk samples divided the study period in two parts. The incidence of new IMI did not differ between the groups (1st part of trial: TG vs. CG: 6.84% vs. 9.16%, 2nd part of trial: 7.78% vs. 7.82%). There were no differences between the treatment groups regarding incidence of clinical mastitis. We detected 0.64 clinical cases per 100 days in the treatment group vs. 0.50 in the control group. The development of SCC was comparable in both groups. Teat skin and teat duct conditions showed variation during the study period. Clinical efficacy of postmilking teat disinfection with a foaming iodophor was comparable to the treatment with a conventional iodophor product.


Propane dehydrogenation: catalyst development, new chemistry, and emerging technologies.
Propylene is an important building block for enormous petrochemicals including polypropylene, propylene oxide, acrylonitrile and so forth. Propane dehydrogenation (PDH) is an industrial technology for direct propylene production which has received extensive attention in recent years. With the development of dehydrogenation technologies, the efficient adsorption/activation of propane and subsequential desorption of propylene on the surfaces of heterogeneous catalysts remain scientifically challenging. This review describes recent advances in the fundamental understandings of the PDH process in terms of emerging technologies, catalyst development and new chemistry in regulating the catalyst structures and inhibiting the catalyst deactivation. The active sites, reaction pathways and deactivation mechanisms of PDH over metals and metal oxides as well as their dependent factors are also analysed and discussed, which is expected to enable efficient catalyst design for minimizing the reaction barriers and controlling the selectivity towards propylene. The challenges and perspectives of PDH over heterogeneous catalysts are also proposed for further development.


Neurocognitive profiles in Salla disease.
Salla disease, a free sialic acid storage disorder, is one of the 36 currently known disorders in Finland that form the Finnish disease heritage. Salla disease leads to learning disability* with a wide clinical variation. Two main categories of the disease have been classified: a conventional subtype and a severe subtype with more severe defects. We present detailed neurocognitive profiles of 41 Finnish patients with Salla disease (19 females, 22 males; age range 11mo to 63y, median 19y). The neurocognitive development of patients with Salla disease was assessed by psychological and neuropsychological testing. All patients were also examined by a paediatric neurologist and a speech therapist. The characteristic cognitive profile consisted of a lower non-verbal performance (mean developmental age 13mo) compared with linguistic skills (mean developmental age 17mo). In particular, spatial and visual-constructive impairments were typical of these patients. Tactile and visual discrimination of forms was poor. Tasks demanding hand-eye coordination, maintenance of visual attention, and those requiring short-term visual memory and executive skills were performed better. Receptive language skills were notably better compared with expressive speech. The patients' interactive and non-verbal communication skills were quite strong. Another typical pattern with Salla disease was severe motor disability. After the second decade of life, the decline in these skills was more pronounced than patients' cognitive deterioration. Our results indicate that even though there is a considerable variation in the clinical findings of patients with Salla disease, the characteristic neurocognitive profile of the disease can be outlined.


Downregulation of miR-382 by propranolol inhibits the progression of infantile hemangioma via the PTEN-mediated AKT/mTOR pathway.
Approximately 10% of infantile hemangiomas (IHs) are the most common vascular tumors affecting children and are characterized by rapid growth, and can have destructive, disfiguring and even life-threatening consequences. Currently, propranolol is considered to be a safe and effective treatment option for problematic proliferating IHs. Recent studies have also revealed that microRNAs (miRNAs or miRs) play important roles in the regulation of angiogenesis. In this study, XPTS‑1 cells were used as a hemangioma-derived endothelial cell line constructed in our laboratory. Through a series of experiments, we discovered that miR‑382 is a novel miRNA associated with IHs, which was overexpressed in XPTS‑1 cells and was conversely downregulated by treatment with propranolol. In addition, we found that miR‑382 contributes to the progression of IHs. Our results revealed that propranolol inhibited XPTS‑1 cell migration and proliferation, and promoted apoptosis, and these effects were reversed by the restoration of miR‑382 expression by transfection of the cells with an miR‑382 overexpression vector. Further experiments revealed that the above-mentioned effects were associated with the phosphatase and tensin homolog (PTEN)-mediated AKT/mammalian target of rapamycin (mTOR) signaling pathway. The expression of PTEN was upregulated, while that of p-AKT, p-mTOR and p-p70S6K was downregulated by propranolol; these effects were partly reversed by the overexpression of miR‑382. On the whole, our study identified that the downregulation of miR‑382 by propranolol inhibits the progression of IHs via the PTEN-mediated AKT/mTOR pathway.


[NAD+-converting enzymes in neuronal and glial cells: CD38 as a novel target for neuroprotection].
The review contains current data on molecular mechanisms which control NAD+ homeostasis in brain cells. It also deals with the role of NAD+-converting enzymes in regulation of functional activity, viability and intercellular communication of neuronal and glial cells. Special attention is paid to involvement of CD38 into regulation of NAD+ levels in brain cells in normal and pathological conditions.


Radiological and anatomical evaluation of the atlantoaxial transarticular screw fixation technique.
Sixty-one patients treated with C1-2 transarticular screw fixation for spinal instability participated in a detailed clinical and radiological study to determine outcome and clarify potential hazards. The most common condition was rheumatoid arthritis (37 patients) followed by traumatic instability (15 patients). Twenty-one of these patients (one-third) underwent either surgical revision for a previously failed posterior fusion technique or a combined anteroposterior procedure. Eleven patients underwent transoral odontoidectomy and excision of the arch of C-1 prior to posterior surgery. No patient died, but there were five vertebral artery (VA) injuries and one temporary cranial nerve palsy. Screw malposition (14% of placements) was comparable to another large series reported by Grob, et al. There were five broken screws, and all were associated with incorrect placement. Anatomical measurements were made on 25 axis bones. In 20% the VA groove on one side was large enough to reduce the width of the C-2 pedicle, thus preventing the safe passage of a 3.5-mm diameter screw. In addition to the obvious dangers in patients with damaged or deficient atlantoaxial lateral mass, the following risk factors were identified in this series: 1) incomplete reduction prior to screw placement, accounting for two-thirds of screw complications and all five VA injuries; 2) previous transoral surgery with removal of the anterior tubercle or the arch of the atlas, thus obliterating an important fluoroscopic landmark; and 3) failure to appreciate the size of the VA in the axis pedicle and lateral mass. A low trajectory with screw placement below the atlas tubercle was found in patients with VA laceration. The technique that was associated with an 87% fusion rate requires detailed computerized tomography scanning prior to surgery, very careful attention to local anatomy, and nearly complete atlantoaxial reduction during surgery.


Surviving acute myocardial infarction: survivin expression in viable cardiomyocytes after infarction.
Apoptosis is a key feature in postinfarction remodelling leading to progressive myocyte loss. Both proapoptotic and antiapoptotic factors contribute to the delicate balance between death and survival. The survivin pathway has emerged as essential in the control of apoptosis, although its role in heart disease is unknown. To evaluate survivin expression after acute myocardial infarction (AMI). Survivin expression was assessed immunohistochemically in the peri-infarct and remote viable myocardium in 17 consecutive patients who died 1-30 weeks after AMI and in four control hearts. Survivin was expressed by myocytes in the peri-infarct area in eight patients and in the remote region in 13 patients. The rate of survivin expression after AMI was significantly higher in the remote versus peri-infarct regions and compared with control hearts. Its expression was inversely associated with the presence of dilated cardiopathy and of apoptosis, independently from the gross pathology infarct size. Survivin myocardial expression after AMI may be associated with the survival of at risk myocardium and may be indicative of more favourable remodelling after AMI. These findings identify a potential new target for the treatment of postinfarction remodelling.


SCE1, the SUMO-conjugating enzyme in plants that interacts with NIb, the RNA-dependent RNA polymerase of Turnip mosaic virus, is required for viral infection.
SUMOylation, which is catalyzed by small ubiquitin-like modifier (SUMO) enzymes, is a transient, reversible posttranslational protein modification that regulates diverse cellular processes. Potyviruses, the largest group of known plant viruses, comprise many agriculturally important viruses, such as Turnip mosaic virus (TuMV). The potyviral genome encodes 11 mature proteins. To investigate if SUMOylation plays a role in potyvirus infection, a yeast two-hybrid screen was performed to examine possible interactions of each of the 11 viral proteins of TuMV with AtSCE1, the only SUMO-conjugating enzyme in Arabidopsis thaliana homologous to the key SUMO-conjugating enzyme E2 in mammalian cells or Ubc9 in yeast. A positive reaction was found between AtSCE1 and NIb, the potyviral RNA-dependent RNA polymerase. Further bimolecular fluorescence complementation (BiFC) and fluorescence resonance energy transfer (FRET) assays revealed that the NIb and AtSCE1 interaction occurred in both the cytoplasm and nuclei of epidermal cells of Nicotiana benthamiana. The interaction motif was mapped to a region encompassing NIb amino acids 171 to 300 which contains a potential negatively charged amino acid-dependent SUMOylation motif (NDSM). An Escherichia coli SUMOylation assay showed that NIb can be SUMOylated and that the lysine residue (K172) in the motif is a potent SUMOylation site. A TuMV infectious clone with an arginine (R) substitution mutation at K172 compromised TuMV infectivity in plants. In comparison with wild-type Arabidopsis plants, sce1 knockdown plants exhibited increased resistance to TuMV as well as a nonrelated RNA virus. To the best of our knowledge, this is the first report showing that the host SUMO modification system plays an essential role in infection by plant RNA viruses.


32-P-HPLC analysis of DNA adducts formed in vitro and in vivo by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, utilizing an improved adduct enrichment procedure.
DNA adducts of 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-diMeIQx), synthesized in vitro with calf thymus DNA and formed in vivo in the male Wistar rat, were enriched from digested DNA by butanol extraction before 32P-postlabeling. The recovery after butanol enrichment was 79% and 32% for in vitro modified PhIP- and 4,8-diMeIQx-DNA adducts, respectively. Crude postlabeling mixtures were chromatographically separated by high-performance liquid chromatography with on-line 32P-detection (32P-HPLC). The major PhIP- and 4,8-diMeIQx-DNA adducts formed in vitro cochromatographed with the respective pdGp-C8 adduct standard. 32P-HPLC was also used to separate hydrolysates of in vitro formed PhIP-DNA and 4,8-diMeIQx-DNA that had been 32P-postlabeled under ATP-deficient conditions. The adduct recovery of the ATP-deficient method relative to the improved butanol enrichment procedure was 29% and 59% for total PhIP-DNA and 4,8-diMeIQx-DNA adducts, respectively. Simplified DNA adduct patterns were obtained when the postlabeling mixtures were incubated with nuclease P1, suggesting incomplete DNA hydrolysis. After nuclease P1 treatment, the major DNA adducts of PhIP and 4,8-diMeIQx formed in vitro cochromatographed with the respective pdG-C8 adduct standard. In vivo PhIP formed what appeared to be multiple DNA adducts; however, after nuclease P1 treatment the PhIP-associated peaks were concentrated into a single peak cochromatographing with pdG-C8-PhIP, 4,8-diMeIQx formed multiple DNA adducts in vivo. Nuclease P1 treatment resulted in two 4,8-diMeIQx related peaks, one cochromatographing with pdG-C8-4,8-diMeIQx. The second peak remains unidentified. The improved workup procedures in combination with the high resolution and reproducibility of the 32P-HPLC system should be useful for characterization of PhIP- and 4,8-diMeIQx-DNA adducts in DNA modified by complex mixtures.


Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise.
Long, uninterrupted bouts of sedentary behavior are thought to negatively influence postprandial glucose and insulin concentrations. We examined the effects of a 1-h bout of morning exercise versus intermittent walking bouts of short duration on glucose excursions and insulin secretion over 12-h. Eleven young, obese individuals (18-35 years, BMI>30kg/m(2)) with impaired glucose tolerance were studied on three 12-h study days: 1) sedentary behavior (SED); 2) sedentary behavior with 1-h morning exercise (EX) at 60%-65% VO2peak; and 3) sedentary behavior with 12-hourly, 5-min intervals of exercise (INT) at 60%-65% VO2peak. Meals (1046kJ/meal) were provided every 2-h. Blood samples were collected every 10 min and measured for glucose, insulin, and c-peptide concentrations. Glucose iAUC (12-h) was attenuated in the INT and SED conditions compared to the EX condition (P<0.05). Glucose concentrations were higher in the EX compared to the SED condition for ~150min (20% of the study day), and comparison of the EX-INT study days revealed that glucose concentrations were greater for~240min (~1/3 of the 12-hday). In the SED condition, the 12-h insulin iAUC was ~15% higher (P<0.05) compared to the INT and EX conditions. Insulin production rate was found to increase ~20% with INT exercise vs. the SED and EX condition (P<0.05). Short, frequent periods of exercise attenuated glucose excursions and insulin concentrations in obese individuals to a greater degree than an equal amount of exercise performed continuously in the morning.


Inhibition by oestrogen of collagen breakdown in the involuting rat uterus.
1. Both the post-partum involution of the rat uterus and the rapid breakdown of collagen that accompanies it are extensively inhibited by oestrogenic hormones. In the normal rat, 85% of the uterine collagen is degraded within 4 days after parturition; in rats treated with 100mug. of 17beta-oestradiol/day, only 35% of uterine collagen is broken down in the same period. 2. Similar effects are produced by diethylstilboestrol if the dose is increased tenfold. 3. Collagen breakdown is inhibited to a greater extent than is the loss of wet weight by oestradiol but not by diethylstilboestrol. 4. The oestrogens appear to act by blocking the breakdown of collagen. There is a greatly decreased concentration of free hydroxyproline in the uterus of treated animals. 5. Acid hydrolase concentrations (beta-glucuronidase, beta-galactosidase, cathepsin D and acid phosphatase) in the uterus are decreased by oestrogen treatment compared with controls, but the total amounts of these enzymes in the uterus are somewhat elevated. Oestrogens do not appear to inhibit collagen breakdown by altering the concentration and total amount of acid hydrolases.


Fifteen-minute consultation: Monogenic forms of diabetes with onset after age 6 months.
Monogenic forms of diabetes (historically known as Maturity Onset Diabetes of the Young (MODY)) are caused by single gene mutations inherited in an autosomal dominant fashion that result in reduced pancreatic beta cell function. Children with these forms of diabetes may be misdiagnosed as having type 1 or 2 diabetes, which has important implications for treatment, genetic counselling, screening of family members and prognosis. Useful tools now exist to aid in their diagnosis and management. Here, we attempt to outline the clinical features that will help the physician make the differentiation from other diabetes subtypes.


Comparison of the impact of closing wedge versus opening wedge high tibial osteotomy on proximal tibial deformity and subsequent revision to total knee arthroplasty.
The purpose of this study was to assess the differences in proximal tibial deformity between closing wedge (CW) and opening wedge (OW) high tibial osteotomy (HTO) and their effects on the difficulty of total knee arthroplasty (TKA) conversion. Surgical simulations of CW-HTO and OW-HTO were performed on the same 3D computer-aided design knee models reconstructed from computed tomographic datasets of patients (median age 77 years; range 55-87 years; 40 knees) with medial osteoarthritis or osteonecrosis, and proximal tibial deformities were analysed. Subsequent TKA conversion was simulated in both CW and OW models, and the interference between the tibial implant and endosteal cortex was assessed. The difference in the metaphyseal-diaphyseal angle in the CW-HTO and OW-HTO groups was 0.3° ± 0.2° (p < 0.001). The mechanical axis in the CW-HTO group was shifted laterally by 1.8 ± 1.1 mm relative to that in the OW-HTO group (p < 0.001) on the resection surface in TKA. Finally, the TKA tibial implant was substantially closer to the endosteal cortex in the CW-HTO group (mean 5.6 ± 1.6 mm) than to that in the OW-HTO group (mean 7.3 ± 1.6 mm) (p < 0.001). The difference in the post-operative angular deformities of the proximal tibia between CW-HTO and OW-HTO was considered to be clinically irrelevant. The risk of interference between TKA tibial implant and endosteal bone was greater after CW-HTO than after OW-HTO. For clinical relevance, the difference between the two techniques has little influence on subsequent TKA difficulty regarding the proximal tibial deformity, although preoperative planning is obligatory, particularly after CW-HTO, to prevent interference with the tibial implant. II.


Regulation of quorum sensing by RpoS in Pseudomonas aeruginosa.
The LasR-LasI and RhlR-RhlI quorum-sensing systems are global regulators of gene expression in the opportunistic pathogen Pseudomonas aeruginosa. Previous studies suggest that the RhlR-RhlI system activates expression of rpoS. We constructed merodiploid strains of P. aeruginosa containing the native rpoS gene and an rpoS-lacZ fusion. Studies of lacZ transcription in these strains indicated that rpoS was not regulated by RhlR-RhlI. We also generated an rpoS null mutant. This rpoS mutant showed elevated levels of rhlI (but not rhlR) transcription, elevated levels of the RhlI-generated acylhomoserine lactone quorum-sensing signal, and elevated levels of RhlR-RhlI-regulated gene transcription. These findings indicate that there is a relationship between RpoS and quorum sensing, but rather than the RhlR-RhlI system influencing the expression of rpoS, it appears that RpoS regulates rhlI.


Stroke pathway performance assessment: a retrospective observational study.
Performance assessment of the Stroke Pathway is a key element in healthcare quality. The aim of this study has been to carry out a retrospective assessment of the Stroke Pathway in a first level Stroke Unit in Italy, analyzing the temporal trend of the Stroke Pathway performance and the impact of the COVID-19 pandemic. A retrospective observational study was carried out analyzing data from 1/01/2010 to 31/12/2020. The following parameters were considered: volume and characteristics of patients with ischemic stroke undergoing intravenous thrombolysis, baseline modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores, Onset-to-Door (OTD), Door-To-Imaging (DTI) and Door-To-Needle (DTN) Times, mRS score 3 months after the ischemic event onset (3 m-mRS) and NIHSS score 24 h after the ischemic event onset (24 h-NIHSS). The study also compared the pre-COVID-19 pandemic period (March-December 2019) with the one immediately following it (March-December 2020). 418 patients were included. Over time, treatment was extended to older patients (mean age from 66.3 to 75.51 years; p = 0.006) and with a higher level of baseline disability (baseline mRS score from 0.22 to 1.22; p = 0.000). A statistically significant reduction over the years was found for DTN, going from 90 min to 61 min (p = 0.000) with also an increase in the number of thrombolysis performed within the "golden hour" - more than 50% in 2019 and more of 60% in 2020. Comparing pre- and during COVID-19 pandemic periods, the number of patients remained almost unchanged, but with a significantly higher baseline disability (mRS = 1.18 vs. 0.72, p = 0.048). The pre-hospital process indicator OTD increased from 88.13 to 118.48 min, although without a statistically significant difference (p = 0.197). Despite the difficulties for hospitals due to pandemic, the hospital process indicators DTI and DTN remained substantially unchanged, as well as the clinical outcome indicators 3 m-mRS, NHISS and 24 h-NHISS. The results of the retrospective assessment of the Stroke Pathway highlighted its positive impact both on hospital processes and patients' outcomes, even during the COVID-19 pandemic, so that the current performance is aligning itself with international goals. Moreover, the analysis showed the need of improvement actions for both hospital and pre-hospital phases. The Stroke Pathway should be improved with the thrombolysis starting in the diagnostic imaging department in order to further reduce the DTN score. Moreover, health education initiatives involving all the stakeholders should be promoted, also by using social media, to increase population awareness on timely recognition of stroke signs and symptoms and emergence medical services usage.


Major changes in microbial diversity and community composition across gut sections of a juvenile Panchlora cockroach.
Investigations of gut microbiomes have shed light on the diversity and genetic content of these communities, and helped shape our understanding of how host-associated microorganisms influence host physiology, behavior, and health. Despite the importance of gut microbes to metazoans, our understanding of the changes in diversity and composition across the alimentary tract, and the source of the resident community are limited. Here, using community metagenomics and 16S rRNA gene sequencing, we assess microbial community diversity and coding potential in the foregut, midgut, and hindgut of a juvenile Panchlora cockroach, which resides in the refuse piles of the leaf-cutter ant species Atta colombica. We found a significant shift in the microbial community structure and coding potential throughout the three gut sections of Panchlora sp., and through comparison with previously generated metagenomes of the cockroach's food source and niche, we reveal that this shift in microbial community composition is influenced by the ecosystems in which Panchlora sp. occurs. While the foregut is composed of microbes that likely originate from the symbiotic fungus gardens of the ants, the midgut and hindgut are composed of a microbial community that is likely cockroach-specific. Analogous to mammalian systems, the midgut and hindgut appear to be dominated by Firmicutes and Bacteroidetes with the capacity for polysaccharide degradation, suggesting they may assist in the degradation of dietary plant material. Our work underscores the prominence of community changes throughout gut microbiomes and highlights ecological factors that underpin the structure and function of the symbiotic microbial communities of metazoans.


Occurrence and diversity of Giardia duodenalis assemblages in livestock in the UK.
Giardia duodenalis is a common intestinal parasite in humans and a wide range of livestock species. It is a genetically heterogeneous parasite that has been characterized in seven distinct genetic assemblages or cryptic species, and molecular markers can be used to differentiate both animal-specific and potentially zoonotic genotypes. Little is known about G. duodenalis and the range of assemblages occurring in domestic livestock species in the UK. Here, we present data on the occurrence and molecular diversity of G. duodenalis detected in the faeces or large intestinal contents of cattle, sheep, pigs, goats and camelids from farms in the north-west of England. Both healthy and clinically diseased animals were included in the survey. The presence of Giardia spp. and assemblages was determined by sequencing of the small-subunit ribosomal RNA gene. The potential association of infection with various clinical and epidemiological parameters was studied in cattle using both univariate and multivariate analyses. Giardia spp. were detected in 127 (34.3%) of the 370 animals tested. G. duodenalis assemblage E was found to be predominant in cattle and sheep, followed by assemblage A. Mixed infections with assemblages A and E were also detected. Interestingly, some cattle, sheep and pigs were found to be infected with more unexpected assemblages (C, D, F). Pre-weaned calves were more likely to test positive than adult animals, but no association between the occurrence of overt intestinal disease and G. duodenalis infection was detected. The common occurrence of assemblage A and the finding of unusual assemblages in atypical hosts suggest that in future, a multilocus analysis should be used to confirm the actual diversity of G. duodenalis in livestock and the presence of potentially zoonotic genotypes. These data also suggest that there is a need to re-evaluate the clinical significance of G. duodenalis infection in livestock.


Secreted frizzled-related protein 1 (SFRP1) protects fibroblasts from ceramide-induced apoptosis.
Secreted frizzled-related proteins (SFRPs) are soluble proteins that have highly restricted tissue distribution. Although not fully understood, a role of SFRP1 in the regulation of apoptosis has been suggested. Our previous study disclosed a much greater level of SFRP1 expression in periodontal ligament fibroblasts (PDLFs), which have been suggested to maintain a reduced level of apoptosis compared with gingival fibroblasts. We have tested the role of SFRP1 in the regulation of fibroblast apoptosis both in vitro and in vivo. Our data showed that SFRP1 was significantly up-regulated in cultured human PDLFs during ceramide-induced apoptosis. In vivo study demonstrated an increased SFRP1 expression in mice periodontal ligament during force-induced apoptosis. While inhibition of endogenous SFRP1 increased the percentage of cell death in cultured human PDLFs, exogenous SFRP1 substantially reduced apoptosis in cultured human gingival fibroblasts, which do not maintain a high level of endogenous SFRP1 expression. The effect of SFRP1 on apoptosis was linked to the regulation of several apoptosis-related genes, including p53, caspase-3, caspase-9, and BCL-2-interacting killer (BIK). Furthermore our results indicated that the addition of exogenous SFRP1 could reduce the level of apoptosis in dermal fibroblasts in vivo, and this effect was also linked to the regulation of similar apoptosis-related genes as observed in in vitro studies. Collectively our results suggest that the constitutive up-regulation of SFRP1 could be an adaptive cell survival mechanism inherent to functionally specialized fibroblasts, and the addition of SFRP1 may contribute to the inhibition of apoptosis in fibroblast-related cells.


Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics.
Recent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients. To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival. Phase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo, and then 80 mg monthly (240/80 mg); degarelix at 240 mg for 1 mo, and then 160 mg monthly; and leuprolide at 7.5 mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer). PSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and ≥ 5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (<10, 10-20, >20-50, and >50 ng/ml) were analysed. Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p=0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p=0.04). The relatively low number of patients in each subgroup is a limitation of this study. These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings.


Scientific Appearance and Homeopathy. Determinants of Trust in Complementary and Alternative Medicine.
Several studies have investigated the motivations driving the use of complementary and alternative medicines (CAM). Nevertheless, the general public view of these therapies remains relatively unexplored. Our study identifies the social factors that determine a person's trust in alternative therapies, like homeopathy or acupuncture, drawing conclusions from the results of the Spanish National Survey on the Social Perception of Science and Technology (N = 6,357). We show that trust in the effectiveness of CAM therapies is not mutually exclusive with a belief in science for the general public, pointing to a certain level of disinformation. The comparison with superstitions confirms a clear differentiation with the drivers of trust in analyzed CAM therapies. We argue that scientific appearance of these alternative therapies, in terms of prescription, communication and marketing, may play an important role in determining trust in them for a large part of the population. Furthermore, we confirm that women and those with higher socio-economic status are more likely to express trust in the effectiveness of CAM therapies. Additionally, distrust of the influence of big pharma on health policies seems to have an effect on viewing CAM therapies as more effective. Finally, we argue that media and pharmacies may have an effect on the scientific-like perception of CAM therapies, contributing to the social construction of trust in its effectiveness. Therefore, widespread confusion about the scientific validation of homeopathy may be among the main factors driving its successful extension as a practice.


[Hidden diseases: tuberculosis in a woman with a severe mental illness].
Patients with severe mental illness often have only limited access to health care for physical symptoms. They have difficulty in organising their thoughts and articulating their requests for medical help; in addition, they often have a reduced perception of stimuli like physical pain. There may also be a language barrier and sometimes a cultural barrier. The case that we present demonstrates that these are not separate causes but they are interrelated in a complex manner. Screening for a latent disease such as tuberculosis reduces the risk of a delayed diagnosis stemming from the patient's inability to articulate a request for medical help. The physical symptoms of patients with severe mental illness can only be reliably interpreted when there is close cooperation between physicians and psychiatrists.


Stereospecificity of the inhibition by etomoxir of fatty acid and cholesterol synthesis in isolated rat hepatocytes.
The racemates of substituted 2-oxiranecarboxylates are potent inhibitors of fatty acid oxidation and fatty acid and cholesterol synthesis. We show in the accompanying paper [Agius L, Peak M and Sherratt HSA, Biochem Pharmacol 42: 1711-1715, 1991] that only the R-enantiomer of etomoxir, a potent hypoglycaemic compound, inhibits fatty acid oxidation in hepatocytes. We demonstrate in this paper that although the R-enantiomer of etomoxir is esterified to its CoA-ester more readily than the S-enantiomer, both the R- and S-enantiomers are equally potent inhibitors of fatty acid and cholesterol synthesis from acetate in rat hepatocytes. The inhibition of fatty acid synthesis is not due to direct inhibition of fatty acid synthetase and the inhibition of cholesterol synthesis occurs at a site proximal to formation of mevalonate. Since the S-enantiomer inhibits fatty acid and cholesterol synthesis but not fatty acid oxidation the inhibition of the biosynthetic pathways is not coupled to inhibition of fatty acid oxidation.


Mental imagery for a conversational robot.
To build robots that engage in fluid face-to-face spoken conversations with people, robots must have ways to connect what they say to what they see. A critical aspect of how language connects to vision is that language encodes points of view. The meaning of my left and your left differs due to an implied shift of visual perspective. The connection of language to vision also relies on object permanence. We can talk about things that are not in view. For a robot to participate in situated spoken dialog, it must have the capacity to imagine shifts of perspective, and it must maintain object permanence. We present a set of representations and procedures that enable a robotic manipulator to maintain a "mental model" of its physical environment by coupling active vision to physical simulation. Within this model, "imagined" views can be generated from arbitrary perspectives, providing the basis for situated language comprehension and production. An initial application of mental imagery for spatial language understanding for an interactive robot is described.


Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL-positive leukemic cells.
Despite promising clinical results from imatinib mesylate and second-generation ABL tyrosine kinase inhibitors (TKIs) for most BCR-ABL(+) leukemia, BCR-ABL harboring the mutation of threonine 315 to isoleucine (BCR-ABL/T315I) is not targeted by any of these agents. We describe the in vitro and in vivo effects of AT9283 (1-cyclopropyl-3[5-morpholin-4yl methyl-1H-benzomidazol-2-yl]-urea), a potent inhibitor of several protein kinases, including Aurora A, Aurora B, Janus kinase 2 (JAK2), JAK3, and ABL on diverse imatinib-resistant BCR-ABL(+) cells. AT9283 showed potent antiproliferative activity on cells transformed by wild-type BCR-ABL and BCR-ABL/T315I. AT9283 inhibited proliferation in a panel of BaF3 and human BCR-ABL(+) cell lines both sensitive and resistant to imatinib because of a variety of mechanisms. In BCR-ABL(+) cells, we confirmed inhibition of substrates of both BCR-ABL (signal transducer and activator of transcription-5) and Aurora B (histone H3) at physiologically achievable concentrations. The in vivo effects of AT9283 were examined in several mouse models engrafted either subcutaneously or intravenously with BaF3/BCR-ABL, human BCR-ABL(+) cell lines, or primary patient samples expressing BCR-ABL/T315I or glutamic acid 255 to lysine, another imatinib-resistant mutation. These data together support further clinical investigation of AT9283 in patients with imatinib- and second-generation ABL TKI-resistant BCR-ABL(+) cells, including T315I.


A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia.
In a previous pilot study, MK-0777--a γ-aminobutyric acid (GABA)(A) α2/α3 partial agonist--was reported to improve delayed memory and cognitive measures of prefrontal cortical function in people with schizophrenia. The current study was designed to further examine the efficacy and safety of MK-0777 for the treatment of cognitive impairments in schizophrenia. Sixty people with DSM-IV schizophrenia entered a 4-week, multi-center, double-blind, placebo-controlled, randomized clinical trial. Participants were randomized to: MK-0777 3 mg b.i.d. (n = 18); MK-0777 8 mg b.i.d. (n = 21); or placebo (n = 21). Participants were clinically stable. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, AX-Continuous Performance Test, and N-Back were used to assess cognition. The University of California San Diego (UCSD) Performance Based Skills Assessment-2 and the Schizophrenia Cognition Rating Scale assessed functional capacity and served as functional outcome coprimary measures. There were no significant group differences on the primary outcome measure, the MATRICS Consensus Cognitive Battery composite score. Secondary analyses suggested that participants randomized to placebo performed significantly better on visual memory and reasoning/problem-solving tests than participants assigned to either MK-0777 dose. There were no significant group differences on the AX-Continuous Performance Test or N-Back d prime scores or UCSD Performance-Based Skills Assessment-2 and Schizophrenia Cognition Rating Scale total scores. In general, MK-0777 was well-tolerated with minimal side effects. The study results suggest that MK-0777 has little benefit for cognitive impairments in people with schizophrenia. The GABA(A) receptor remains a promising target, but a more potent partial agonist with greater intrinsic activity at the GABA(A) α2 site might be needed for cognitive enhancement in schizophrenia.


Compromised communication: a qualitative study exploring Afghan families and health professionals' experience of interpreting support in Australian maternity care.
Difficulties associated with communication are thought to contribute to adverse perinatal outcomes experienced by refugee background women living in developed countries. This study explored Afghan women and men's experience of language support during pregnancy, labour and birth, and health professionals' experiences of communicating with clients of refugee background with low English proficiency. Interviews were conducted with (1) Afghan women and men in the first year after having a baby in Australia, by multilingual, bicultural researchers and (2) midwives and medical practitioners providing care to families of refugee background. Analysis was conducted thematically. Sixteen Afghan women, 14 Afghan men, 10 midwives, five medical practitioners and 19 community-based health professionals (refugee health nurses, bicultural workers, counsellors) providing maternity or early postnatal care participated. Midwife and medical informants concurred that accredited interpreters are generally booked for the first pregnancy visit, but not routinely used for other appointments. Very few Afghan participants reported access to on-site interpreters. Men commonly interpreted for their wives. There was minimal professional interpreting support for imaging and pathology screening appointments or during labour and birth. Health professionals noted challenges in negotiating interpreting services when men were insistent on providing language support for their wives and difficulties in managing interpreter-mediated visits within standard appointment times. Failure to engage interpreters was apparent even when accredited interpreters were available and at no cost to the client or provider. Improving identification of language needs at point of entry into healthcare, developing innovative ways to engage interpreters as integral members of multidisciplinary healthcare teams and building health professionals' capacity to respond to language needs are critical to reducing social inequalities in maternal and child health outcomes for refugee and other migrant populations.


The use of lumbar extension in the evaluation and treatment of patients with acute herniated nucleus pulposus. A preliminary report.
Many patients with acute herniated nucleus pulposus can be expected to resolve their conditions with conservative management. To date, however, no reliable sign has been described in the literature that can predict which patient will respond. This report shows that the ability to achieve normal lumbar extension represents such a sign. Of 67 patients who met the criteria for inclusion in the study, 35 patients were treated without operation; 97% were able to achieve normal lumbar extension within three days of admission to the hospital. Thirty-two patients underwent laminotomy and discectomy because they failed to improve with conservative measures. Of these patients, only two (6%) were able to achieve normal lumbar extension preoperatively. Furthermore, some of these patients responded so dramatically to extension therapy that the use of extension exercises as a therapeutic modality is recommended.


Lamin A Ser404 is a nuclear target of Akt phosphorylation in C2C12 cells.
Akt/PKB is a central activator of multiple signaling pathways coupled with a large number of stimuli. Although both localization and activity of Akt in the nuclear compartment are well-documented, most Akt substrates identified so far are located in the cytoplasm, while nuclear substrates have remained elusive. A proteomic-based search for nuclear substrates of Akt was undertaken, exploiting 2D-electrophoresis/MS in combination with an anti-Akt phosphosubstrate antibody. This analysis indicated lamin A/C as a putative substrate of Akt in C2C12 cells. In vitro phosphorylation of endogenous lamin A/C by recombinant Akt further validated this result. Moreover, by phosphopeptide analysis and point mutation, we established that lamin A/C is phosphorylated by Akt at Ser404, in an evolutionary conserved Akt motif. To delve deeper into this, we raised an antibody against the lamin A Ser404 phosphopeptide which allowed us to determine that phosphorylation of lamin A Ser404 is triggered by the well-known Akt activator insulin, and is therefore to be regarded as a physiological response. Remarkably, expression of S404A lamin A in primary cells from healthy tissue caused the nuclear abnormalities that are a hallmark of Emery-Dreifuss muscular dystrophy (EDMD) cells. Indeed, it is known that mutations at several sites in lamin A/C cause autosomal dominant EDMD. Very importantly, we show here that Akt failed to phosphorylate lamin A/C in primary cells from an EDMD-2 patient with lamin A/C mutated in the Akt consensus motif. Together, our data demonstrate that lamin A/C is a novel signaling target of Akt, and implicate Akt phosphorylation of lamin A/C in the correct function of the nuclear lamina.


Molecular characterisation of a cDNA sequence encoding the backbone of a style-specific 120 kDa glycoprotein which has features of both extensins and arabinogalactan proteins.
Nicotiana alata has a style-specific hydroxyproline-rich glycoprotein (the 120 kDa glycoprotein) which has properties of both extensins and AGPs [19, 20]. The 120 kDa glycoprotein is a soluble component in the extracellular matrix of the transmitting tract of styles where it accounts for ca. 9% of the total buffer-soluble protein. Here we describe the molecular cloning of a cDNA representing the gene NaPRP5 which encodes the backbone of the 120 kDa glycoprotein. Expression of mRNA is restricted to styles, consistent with observations on the distribution of the 120 kDa glycoprotein. Levels of accumulation of the transcript encoding the 120 kDa protein backbone are not altered significantly by pollination with either compatible or incompatible pollen. The protein backbone of the 120 kDa glycoprotein, as predicted by the cDNA sequence, is composed of three distinct domains. The sequence of these domains, together with linkage analysis of the carbohydrate component of the 120 kDa glycoprotein, allows predictions of the likely distribution of substituent glycosyl chains along the protein backbone. The similarity of the C-terminal domains of the 120 kDa glycoprotein and GaRSGP, the galactose-rich style glycoprotein of N. alata, is consistent with the two molecules sharing a common antigenic domain in their backbones [31]. The sharing of domains between distinct hydroxyproline-rich glycoproteins suggests that identification of a glycoprotein of this class solely by its protein or carbohydrate epitope is not valid.


Determination of pethidine hydrochloride using potentiometric coated graphite and carbon paste electrodes.
A new approach for lowering the detection limit of a pethidine ion-selective electrode is presented. A coated graphite (CGE) and carbon paste (CPE) electrodes for pethidine ions based on pethidine-phosphotungstate (PD-PT) as ion-pair complex are described. The sensors exhibit a Nernstian slope of 58.1 and 54.2 mVdecade(-1) for pethidine ion over a wide concentration range from 2.6 × 10(-7) to 1.0 × 10(-2) M and 2.1 × 10(-6) to 1.0 × 10(-2) M with a detection limit of 1.8 × 10(-7) M and 7.3 × 10(-7) M for pethidine coated graphite (PD-CGE) and pethidine carbon paste electrode (PD-CPE), respectively. These sensors exhibited a fast response time (about 5-8 s) and good stability. The standard electrode potentials, E(o) , were determined at different temperatures and used to calculate the isothermal temperature coefficient (dE(o) /dT) of the PD-CGE and PD-CPE, which was 0.0062 and 0.0071 V/ °C, respectively. Selectivity coefficients, determined by matched potential method (MPM) and separate solution method (SSM), showed high selectivity for pethidine hydrochloride (PDCl) over a large number of inorganic cations, organic cations, sugars, urine components, and some common drug excipients. The sensors were applied for determination of PDCl in ampoule and in spiked urine samples using potentiometric determination, standard addition and the calibration curve methods. The results obtained were satisfactory with excellent percentage recovery comparable and sometimes better than those obtained by other routine methods for the assay.


[Diagnosis of familial amyloid polyneuropathy type I in Argentina].
Familial amyloid polyneuropathy (FAP) is an autosomal dominant inherited disease, characterized by systemic deposition of amyloid fibrils in various tissues, especially in peripheral nerves, being a variant of transthyretin (TTR) the principal component of amyloid fibrils. TTR is a normal plasma protein (previously called prealbumin) that functions as a transport protein binding tiroxine and retinol. Among many mutations that have been found in the TTR gene, the variant with a single amino acid substitution of methionine for valine at position 30 (TTR Val30Met) is the responsible of the Portuguese-type Familial Amyloidotic Polyneuropathy (FAP Type I). Interest in this pathology has arisen in Argentina because of the finding of an endemic area where a group of Portuguese immigrant families is localized. Since liver transplantation is a widely accepted treatment because it results in the disappearance of variant transthyretin from plasma, an early detection of the altered gene is essential. Thus, the objective of the present work was to optimize a methodology to detect the Val30Met mutation introducing modifications into techniques that were previously developed. The simple method here described is useful to confirm the diagnosis of the potential disease and, therefore, make it possible for patients to gain access to early liver transplantation.


A cis-regulatory mutation in troponin-I of Drosophila reveals the importance of proper stoichiometry of structural proteins during muscle assembly.
Rapid and high wing-beat frequencies achieved during insect flight are powered by the indirect flight muscles, the largest group of muscles present in the thorax. Any anomaly during the assembly and/or structural impairment of the indirect flight muscles gives rise to a flightless phenotype. Multiple mutagenesis screens in Drosophila melanogaster for defective flight behavior have led to the isolation and characterization of mutations that have been instrumental in the identification of many proteins and residues that are important for muscle assembly, function, and disease. In this article, we present a molecular-genetic characterization of a flightless mutation, flightless-H (fliH), originally designated as heldup-a (hdp-a). We show that fliH is a cis-regulatory mutation of the wings up A (wupA) gene, which codes for the troponin-I protein, one of the troponin complex proteins, involved in regulation of muscle contraction. The mutation leads to reduced levels of troponin-I transcript and protein. In addition to this, there is also coordinated reduction in transcript and protein levels of other structural protein isoforms that are part of the troponin complex. The altered transcript and protein stoichiometry ultimately culminates in unregulated acto-myosin interactions and a hypercontraction muscle phenotype. Our results shed new insights into the importance of maintaining the stoichiometry of structural proteins during muscle assembly for proper function with implications for the identification of mutations and disease phenotypes in other species, including humans.


Lack of efficacy of a double autograft program to prolong survival of chronic myelogenous leukemia patients in blastic transformation.
The prognosis of patients in blast crisis of chronic myelogenous leukemia treated with conventional polychemotherapy is extremely poor. Autologous blood stem cell transplantation has been proposed by several authors, and the possibility of achieving a second chronic phase (CP), albeit very short lived, has been reported. In our study, we evaluated the feasibility and efficacy of a double sequential autograft program utilizing two different conditioning regimens. Nine patients underwent the first autograft, but only three were eligible for the second because of one early death, four relapses and one patient who underwent mismatched alloBMT. Of the three patients receiving the second graft, we observed 2 toxic deaths and one relapse six months after transplantation. We conclude that our experience with double autograft in this phase of the disease is very disappointing. since it was associated with prohibitive toxicity in the absence of any advantages in terms of survival for these patients.


Hip spine relationships: application to total hip arthroplasty.
Lumbo-sacral orientation in the sagittal plane is of utmost importance, as it plays a critical role in the function of the spine and the hip joints. Equilibrium of the trunk influences the tridimensional orientation of the acetabulum and the functional range of motion of the hips. Each patient is characterized by a "morphological" parameter named incidence angle; its sagittal balance is the consequence of a postural adaptation for other functional parameters (pelvic tilt, sacral slope, lumbar lordosis, acetabular sagittal tilt, functional anteversion). Understanding variations of the sacral slope on lateral pelvic X-rays is essential for planning total hip arthroplasty and identifying patients at risk of impingement, as lumbosacral posture influences functional anteversion of the acetabulum. Posterior pelvic version as in sitting position (sacral slope decrease) is linked to the increase of the functional acetabular anteversion. Anterior pelvic version as in standing position (sacral slope increase) is linked to the decrease of the functional acetabular anteversion.


Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS.
The antioxidant enzyme Cu,Zn-superoxide dismutase (SOD1) has the distinction of being one of the most abundant disulfide-containing protein known in the eukaryotic cytosol; however, neither catalytic nor physiological roles for the conserved disulfide are known. Here we show that the disulfide status of Saccharomyces cerevisiae SOD1 significantly affects the monomer-dimer equilibrium, the interaction with the copper chaperone CCS, and the activity of the enzyme itself. Disulfide formation in SOD1 by O2 is slow but is greatly accelerated by the Cu-bound form of CCS (Cu-CCS) in vivo and in vitro even in the presence of excess reductants; once formed, this disulfide is kinetically stable. Biochemical assays reveal that Cu-CCS facilitates Cys oxidation and disulfide isomerization in the stepwise conversion of the immature form of the enzyme to the active state. The immature form of SOD1 is most susceptible to oxidative insult and to aggregation reminiscent of that observed in amyotrophic lateral sclerosis. Thus Cu-CCS mediation of correct disulfide formation in SOD1 is important for regulation of enzyme activity and for prevention of misfolding or aggregation.


Efficient Production of Poly(Cyclohexene Carbonate) via ROCOP of Cyclohexene Oxide and CO2 Mediated by NNO-Scorpionate Zinc Complexes.
New mono- and dinuclear chiral alkoxide/thioalkoxide NNO-scorpinate zinc complexes were easily synthesized in very high yields, and characterized by spectroscopic methods. X-ray diffraction analysis unambiguously confirmed the different nuclearity of the new complexes as well as the variety of coordination modes of the scorpionate ligands. Scorpionate zinc complexes 2, 4 and 6 were assessed as catalysts for polycarbonate production from epoxide and carbon dioxide with no need for a co-catalyst or activator under mild conditions. Interestingly, at 70 °C, 10 bar of CO2 pressure and 1 mol % of loading, the dinuclear thioaryloxide [Zn(bpzaepe)2{Zn(SAr)2}] (4) behaves as an efficient and selective one-component initiator for the synthesis of poly(cyclohexene carbonate) via ring-opening copolymerization of cyclohexene oxide (CHO) and CO2, affording polycarbonate materials with narrow dispersity values.


Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading.
Sclerostin, the Wnt signaling antagonist encoded by the Sost gene, is secreted by osteocytes and inhibits bone formation by osteoblasts. Mechanical stimulation reduces sclerostin expression, suggesting that osteocytes might coordinate the osteogenic response to mechanical force by locally unleashing Wnt signaling. To investigate whether sclerostin downregulation is a pre-requisite for load-induced bone formation, we conducted experiments in transgenic mice (TG) engineered to maintain high levels of SOST expression during mechanical loading. This was accomplished by introducing a human SOST transgene driven by the 8 kb fragment of the DMP1 promoter that also provided osteocyte specificity of the transgene. Right ulnae were subjected to in vivo cyclic axial loading at equivalent strains for 1 min/day at 2 Hz; left ulnae served as internal controls. Endogenous murine Sost mRNA expression measured 24 h after 1 loading bout was decreased by about 50% in TG and wild type (WT) littermates. In contrast, human SOST, only expressed in TG mice, remained high after loading. Mice were loaded on 3 consecutive days and bone formation was quantified 16 days after initiation of loading. Periosteal bone formation in control ulnae was similar in WT and TG mice. Loading induced the expected strain-dependent increase in bone formation in WT mice, resulting from increases in both mineralizing surface (MS/BS) and mineral apposition rate (MAR). In contrast, load-induced bone formation was reduced by 70-85% in TG mice, due to lower MS/BS and complete inhibition of MAR. Moreover, Wnt target gene expression induced by loading in WT mice was absent in TG mice. Thus, downregulation of Sost/sclerostin in osteocytes is an obligatory step in the mechanotransduction cascade that activates Wnt signaling and directs osteogenesis to where bone is structurally needed.


Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population.
The genetic basis of cardiovascular disease (CVD) with its complex etiology is still largely elusive. Plasma levels of lipids and apolipoproteins are among the major quantitative risk factors for CVD and are well-established intermediate traits that may be more accessible to genetic dissection than clinical CVD end points. Chromosome 19 harbors multiple genes that have been suggested to play a role in lipid metabolism and previous studies indicated the presence of a quantitative trait locus (QTL) for cholesterol levels in genetic isolates. To establish the relevance of genetic variation at chromosome 19 for plasma levels of lipids and apolipoproteins in the general, out-bred Caucasian population, we performed a linkage study in four independent samples, including adolescent Dutch twins and adult Dutch, Swedish and Australian twins totaling 493 dizygotic twin pairs. The average spacing of short-tandem-repeat markers was 6-8 cM. In the three adult twin samples, we found consistent evidence for linkage of chromosome 19 with LDL cholesterol levels (maximum LOD scores of 4.5, 1.7 and 2.1 in the Dutch, Swedish and Australian sample, respectively); no indication for linkage was observed in the adolescent Dutch twin sample. The QTL effects in the three adult samples were not significantly different and a simultaneous analysis of the samples increased the maximum LOD score to 5.7 at 60 cM pter. Bivariate analyses indicated that the putative LDL-C QTL also contributed to the variance in ApoB levels, consistent with the high genetic correlation between these phenotypes. Our study provides strong evidence for the presence of a QTL on chromosome 19 with a major effect on LDL-C plasma levels in outbred Caucasian populations.


The Relative Effects of Artemether-lumefantrine and Non-artemisinin Antimalarials on Gametocyte Carriage and Transmission of Plasmodium falciparum: A Systematic Review and Meta-analysis.
Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely-deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption. We searched electronic databases for randomized controlled trials comparing AL to non-ACTs that reported gametocyte counts or results of mosquito-feeding assays. Two authors working independently assessed eligibility, extracted data, and evaluated the risk of bias. We conducted meta-analyses using a random-effects model. We identified 22 eligible trials. The pooled odds of gametocytemia at 1 week were lower in AL- compared to non-ACT-treated participants (odds ratio [OR] 0.09; 95% confidence interval [CI], 0.06-0.15; I2 = 0.60, P < .01; 15 trials). The odds of transmission to mosquitoes were also lower in AL treatment groups (OR 0.06; 95% CI, 0.00-0.47, P < .01 at 7 days post-treatment; 1 trial; OR 0.56; 95% CI, 0.36-0.88, P = .01 at 14 days post-treatment; 1 trial). AL is superior to non-ACTs in reducing gametocytemia, and, based on limited evidence, abating transmission to mosquitoes. The transmission-limiting benefit of AL has relevance for policymakers planning optimal utilization of control strategies, including use of ACTs for malaria treatment and chemoprevention.


Inert gas bubble formation in magnetron sputtered thin-film CdTe solar cells.
Cadmium telluride (CdTe) solar cells are deposited in current production using evaporation-based tech- niques. Fabricating CdTe solar cells using magnetron sputtering would have the advantage of being more cost-efficient. Here, we show that such deposition results in the incorporation of the magnetron working gas Ar, within the films. Post deposition processing with CdCl2 improves cell efficiency and during which stacking faults are removed. The Ar then accumulates into clusters leading to the creation of voids and blisters on the surface. Using molecular dynamics, the penetration threshold energies are determined for both Ar and Xe, with CdTe in both zinc-blende and wurtzite phases. These calculations show that more Ar than Xe can penetrate into the growing film with most penetration across the (111) surface. The mechanisms and energy barriers for interstitial Ar and Xe diffusion in zinc-blende are determined. Barriers are reduced near existing clusters, increasing the probability of capture-based cluster growth. Barriers in wurtzite are higher with non-Arrhenius behaviour observed. This provides an explanation for the increase in the size of voids observed after stacking fault removal. Blister exfoliation was also modelled, showing the formation of shallow craters with a raised rim.


Timing of Radioactive Iodine Administration Does Not Influence Outcomes in Patients with Differentiated Thyroid Carcinoma.
Radioactive iodine (RAI) is widely used in the management of differentiated thyroid cancer (DTC). The impact of the time interval between total thyroidectomy (TT) and RAI administration on disease outcome remains controversial. The objective of the present study was to evaluate the impact of the time interval between TT and RAI. This study evaluated a cohort of DTC patients who received RAI therapy for whom data on disease status were available. Patients were allocated to one of two groups, according to the time interval between TT and RAI. "Disease-free" was defined as no clinical, imaging, or biochemical evidence of thyroid cancer. The study included 545 individuals. The TNM stages were: 322 (59.1%) patients in Stage I, 62 (11.4%) in Stage II, 65 (11.9%) in Stage III, and 82 (15.0%) in Stage IV. The median time interval between TT and RAI was six months (P25-75: 3-10 months). Patients were allocated to one of two groups according to RAI timing administration: group A ≤6 months after TT (median 3 months; n = 295), or group B >6 months after TT (median 10.5 months; n = 250). There were no differences for sex, histological type, tumor size, distant metastasis, or RAI dose between the groups (p > 0.1). Patients in group B were older (47.1 vs. 43.1 years; p = 0.02), had less cervical metastasis (73.6% vs. 59.3%; p = 0.002), and were more commonly classified as low ATA risk (48.0% vs. 36.6%; p = 0.027). One year after initial therapy, 59.3% and 65.6% of patients in groups A and B, respectively, were considered disease-free (p = 0.15). Remarkably, the percentage of patients classified as disease-free was similar, even when analyzing a subgroup of high-risk patients (n = 72; 9.5% vs. 10.0%; p = 1.0). These findings did not change after a median of six years of follow-up. Accordingly, further analysis by multiple logistic regression showed that timing of RAI was not associated with persistent disease (relative risk 0.97 [confidence interval 0.80-1.19]). Timing of RAI does not seem to interfere with the disease outcomes in DTC and can therefore be safely planned while taking into account the health system logistics.


Enhanced rates of detection and treatment of depression and anxiety disorders among adult patients with epilepsy using automated EMR-based screening.
Depression and anxiety disorders are common among patients with epilepsy (PWE). These comorbidities have been shown to influence prognosis and may have a greater impact on quality of life than seizure control. Despite guideline recommendations and expert consensus to regularly screen for and treat both conditions, there is evidence that they are underdiagnosed and undertreated. Our goal was to test a novel screening method to determine if it would increase the rate of detecting and treating depression and anxiety disorders among PWE. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Brief Epilepsy Anxiety Survey Instrument (brEASI) were selected as validated screening instruments for depression and anxiety disorders, respectively. They were sent via an electronic medical record-linked patient portal to all patients of four epileptologists 48 h prior to their clinic appointment. We evaluated whether this increased the rate of detecting and treating depression and anxiety disorders relative to a historical control group. A total of 563 patients were included of whom 351 were sent the screening instruments. 62.7% of patients completed the screening instruments of whom 47.7% screened positive for either depression only (16.4%), anxiety disorders only (5.5%) or both (25.9%); a statistically significant increase relative to the control group. There was also a significantly increased proportion of patients for whom treatment was initiated for depression (p < 0.01), anxiety disorders (p < 0.01), or both (p < 0.01). We identified an easily applicable and efficient means of enhancing detection and treatment rates for depression and anxiety disorders among PWE in a busy clinic setting.


Buffalo (Bubalus bubalis) ES cell-like cells are capable of in vitro skeletal myogenic differentiation.
When buffalo embryonic stem (ES) cell-like cells that expressed surface markers SSEA-4, TRA-1-60, TRA-1-81, CD9 and CD90 and intracellular markers OCT4, SOX2 and FOXD3, as shown by immunofluorescence, and that expressed REX-1 and NUCLEOSTEMIN as confirmed by RT-PCR, were subjected to suspension culture in hanging drops in absence of LIF and buffalo foetal fibroblast feeder layer support, they differentiated to form three-dimensional embryoid bodies (EBs). Of 231 EBs examined on Day 3 of suspension culture, 141 (61.3 ± 3.09%) were of compact type, whereas 90 (38.4 ± 3.12%) were of cystic type. The cells obtained from EBs were found to express NF-68 and NESTIN (ectodermal lineage), BMP-4 and α-skeletal actin (mesodermal lineage), and α-fetoprotein, GATA-4 and HNF-4 (endodermal lineage). When these EBs were cultured on gelatin-coated dishes, they spontaneously differentiated to several cell types such as epithelial- and neuron-like cells. When EBs were cultured in the presence of 1 or 2% DMSO or 10(-8) M or 10(-7) M retinoic acid for 25 days, ES cells could be directed to form muscle cell-like cells, the identity of which was confirmed by expression of α-actinin by immunofluorescence and of MYF-5, MYOD and MYOGENIN genes by RT-PCR. MYOD was first detected on Day 10 in both treatment groups and on Day 15 in controls, whereas MYOGENIN was first detected on Day 10, Day 15 and Day 25 in the presence of retinoic acid, in the presence of DMSO and in controls, respectively. The present study demonstrates the ability of buffalo ES cell-like cells to undergo directed differentiation to cells of skeletal myogenic lineage.


Dependence of kinetic friction on velocity: master equation approach.
We investigate the velocity dependence of kinetic friction with a model that makes minimal assumptions on the actual mechanism of friction so that it can be applied at many scales, provided the system involves multicontact friction. Using a recently developed master equation approach, we investigate the influence of two concurrent processes. First, at a nonzero temperature, thermal fluctuations allow an activated breaking of contacts that are still below the threshold. As a result, the friction force monotonically increases with velocity. Second, the aging of contacts leads to a decrease of the friction force with velocity. Aging effects include two aspects: the delay in contact formation and aging of a contact itself, i.e., the change of its characteristics with the duration of stationary contact. All these processes are considered simultaneously with the master equation approach, giving a complete dependence of the kinetic friction force on the driving velocity and system temperature, provided the interface parameters are known.


Hydrogen transfer between ethanol molecules during oxidoreduction in vivo.
Rates of exchange catalysed by alcohol dehydrogenase were determined in vivo in order to find rate-limiting steps in ethanol metabolism. Mixtures of [1,1-2H2]- and [2,2,2-2H3]ethanol were injected in rats with bile fistulas. The concentrations in bile of ethanols having different numbers of 2H atoms were determined by g.l.c.-m.s. after the addition of [2H6]ethanol as internal standard and formation of the 3,5-dinitrobenzoates. Extensive formation of [2H4]ethanol indicated that acetaldehyde formed from [2,2,2-2H3]ethanol was reduced to ethanol and that NADH used in this reduction was partly derived from oxidation of [1,1-2H2]ethanol. The rate of acetaldehyde reduction, the degree of labelling of bound NADH and the isotope effect on ethanol oxidation were calculated by fitting models to the found concentrations of ethanols labelled with 1-42H atoms. Control experiments with only [2,2,2-2H3]ethanol showed that there was no loss of the C-2 hydrogens by exchange. The isotope effect on ethanol oxidation appeared to be about 3. Experiments with (1S)-[1-2H]- and [2,2,2-2H3]ethanol indicated that the isotope effect on acetaldehyde oxidation was much smaller. The results indicated that both the rate of reduction of acetaldehyde and the rate of association of NADH with alcohol dehydrogenase were nearly as high as or higher than the net ethanol oxidation. Thus, the rate of ethanol oxidation in vivo is determined by the rates of acetaldehyde oxidation, the rate of dissociation of NADH from alcohol dehydrogenase, and by the rate of reoxidation of cytosolic NADH. In cyanamide-treated rats, the elimination of ethanol was slow but the rates in the oxidoreduction were high, indicating more complete rate-limitation by the oxidation of acetaldehyde.


A Web-Based Tool for a Complete Evaluation of Fragility in Senior Hiv+ Patients.
after the discovery of the antiretroviral therapy, life expectancy of HIV+ patient has become longer and this meant that he would start ageing. International literature demonstrated that the HIV+ patient is more fragile than any other person of the same age and that doesn't present the viral infection. design, development and test of a new web-based instrument to allow the self-administration of the new questionnaire SELFY MPI created during the European project Effichronic. Materials & Methods: between June and September 2018, a group of senior 50 HIV+ patients, was involved. The questionnaire SELFY MPI enables to collect data about quality of life and cognitive functions. the developed web-instrument collects pseudo-anonymous data into the Liguria HIV Network database. The subsequent statistical analysis highlighted a correlation between the two outcomes of SELFY MPI and the laboratory exam's parameter TCD4+ and viral load. the great potentiality of this instrument is not only the support given to clinical research about the effects of HIV on chronical disease management but it can be also used as a follow-up instrument to evaluate different aspects of the geriatric patient life during the years.


In situ scanning tunneling microscopy of corrosion of silver-gold alloys.
An in situ scanning tunneling microscope (STM) was used to observe the morphological changes accompanying the selective dissolution of Ag from low-Ag content Ag-Au alloys in dilute perchloric acid. This study was undertaken to explore the role of surface diffusion in alloy corrosion processes. These results are interpreted within the framework of the kink-ledge-terrace model of a crystal surface and a recent model of alloy corrosion based on a variant of percolation theory. The corrosion process leads to roughening of the surface by dissolution of Ag atoms from terrace sites. Annealing or smoothening of the surface occurs by vacancy migration through clusters and the subsequent annihilation of clusters at terrace ledges.


Multi-criteria ranking and receptor modelling of airborne fine particles at three sites in the Pearl River Delta region of China.
The multi-criteria decision making methods, Preference Ranking Organization METHods for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA), and the two-way Positive Matrix Factorization (PMF) receptor model were applied to airborne fine particle compositional data collected at three sites in Hong Kong during two monitoring campaigns held from November 2000 to October 2001 and November 2004 to October 2005. PROMETHEE/GAIA indicated that the three sites were worse during the later monitoring campaign, and that the order of the air quality at the sites during each campaign was: rural site>urban site>roadside site. The PMF analysis on the other hand, identified 6 common sources at all of the sites (diesel vehicle, fresh sea salt, secondary sulphate, soil, aged sea salt and oil combustion) which accounted for approximately 68.8±8.7% of the fine particle mass at the sites. In addition, road dust, gasoline vehicle, biomass burning, secondary nitrate, and metal processing were identified at some of the sites. Secondary sulphate was found to be the highest contributor to the fine particle mass at the rural and urban sites with vehicle emission as a high contributor to the roadside site. The PMF results are broadly similar to those obtained in a previous analysis by PCA/APCS. However, the PMF analysis resolved more factors at each site than the PCA/APCS. In addition, the study demonstrated that combined results from multi-criteria decision making analysis and receptor modelling can provide more detailed information that can be used to formulate the scientific basis for mitigating air pollution in the region.


Interpretable Machine Learning Framework Reveals Robust Gut Microbiome Features Associated With Type 2 Diabetes.
To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features. We used an interpretable machine learning framework to identify the type 2 diabetes-related gut microbiome features in the cross-sectional analyses of three Chinese cohorts: one discovery cohort (n = 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1: n = 203, 48 cases; cohort 2: n = 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites (n = 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS-type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS (n = 1,832). The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23-1.33), 1.23 (1.13-1.34), and 1.12 (1.06-1.18) across three cohorts. The MRS was positively associated with future glucose increment (P < 0.05) and was correlated with a variety of gut microbiota-derived blood metabolites. Animal study further confirmed the MRS-type 2 diabetes relationship. Body fat distribution was found to be a key factor modulating the gut microbiome-type 2 diabetes relationship. Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.


Leukocytoclastic Vasculitis and Dermal Perivascular Hemophagocytosis Associated With Adalimumab Therapy for Rheumatoid Arthritis.
Tumor necrosis factor (TNF)-α inhibitors target TNF-α to effectively treat autoimmune inflammatory conditions, such as rheumatoid arthritis. However, many cases of cutaneous and systemic vasculitis related to TNF-α inhibitors have been reported in the literature. Here, the authors report the first case of a 61-year-old Japanese woman who developed leukocytoclastic vasculitis with cutaneous perivascular hemophagocytosis, which was related to elevated cytokines and immune complexes after initiating adalimumab for rheumatoid arthritis without evidence of hemophagocytic syndrome and rarely encountered in the skin. The patient was successfully treated by discontinuing adalimumab and initiating corticosteroid therapy, which should be considered as the treatment of choice. We believe that our case confirms and adds to the evidence pertaining to the involvement of TNF-α in dermal perivascular hemophagocytosis, a histologic finding rarely observed in the skin.


A validated, transitional and translational porcine model of hepatocellular carcinoma.
Difficult questions are confronting clinicians attempting to improve hepatocellular carcinoma (HCC) outcomes. A large animal model with genetic, anatomical, and physiological similarities to humans is required to transition from mouse models to human clinical trials to address unmet clinical needs. To validate our previously reported inducible porcine cancer model (Oncopig) as a transitional HCC model, Oncopig hepatocyte cultures were transformed using Cre recombinase. The resulting porcine HCC cells (pHCC) expressed oncogenic TP53R167H and KRASG12D, and displayed nuclear pleomorphisms with pale to granular cytoplasm arranged in expanded plates similar to human HCC histopathology. Human HCC transcriptional hallmarks were detected in pHCC cells using RNA-seq, including TERT reactivation, apoptosis evasion, angiogenesis activation, and Wnt signaling activation. Master regulators of gene expression were conserved across Oncopig and 18 human HCC cell lines. pHCC injection into SCID mice resulted in tumors recapitulating human HCC characteristics, including thick trabeculae formation, pseudoacini patterning, and sheets of well-vascularized stroma. Finally, autologous injection of pHCC cells subcutaneously yielded a tumor histologically characterized as Edmondson Steiner (HCC nuclear grade assessment system) grade 2 HCC with trabecular patterning and T-lymphocyte infiltration. These data demonstrate the Oncopig HCC model's utility for improving detection, treatment, and biomarker discovery relevant to human HCC.


Neural substrates of individual differences in learning generalization via combined brain stimulation and multitasking training.
A pervasive limitation in cognition is reflected by the performance costs we experience when attempting to undertake two tasks simultaneously. While training can overcome these multitasking costs, the more elusive objective of training interventions is to induce persistent gains that transfer across tasks. Combined brain stimulation and cognitive training protocols have been employed to improve a range of psychological processes and facilitate such transfer, with consistent gains demonstrated in multitasking and decision-making. Neural activity in frontal, parietal, and subcortical regions has been implicated in multitasking training gains, but how the brain supports training transfer is poorly understood. To investigate this, we combined transcranial direct current stimulation of the prefrontal cortex and multitasking training, with functional magnetic resonance imaging in 178 participants. We observed transfer to a visual search task, following 1 mA left or right prefrontal cortex transcranial direct current stimulation and multitasking training. These gains persisted for 1-month post-training. Notably, improvements in visual search performance for the right hemisphere stimulation group were associated with activity changes in the right hemisphere dorsolateral prefrontal cortex, intraparietal sulcus, and cerebellum. Thus, functional dynamics in these task-general regions determine how individuals respond to paired stimulation and training, resulting in enhanced performance on an untrained task.


[Sarcoma: tumour banks and evolution of diagnostic procedures].
Regional tumour banks are nowadays an important tool for the management of patients with a sarcoma. Centralized databases with information on frozen or paraffin-embedded tumour samples are necessary tools for clinical and biological research projects for rare tumours and particularly sarcomas. Diagnostic procedures have evolved during the last years with a multidisciplinary management of patients by a national and structured network specialized in sarcomas, a common use of core needle biopsies, a daily use of immunohistochemistry and molecular analyses and the implementation of standardized and structured reports.


[Psychoanalysis and group dynamics as a method of socialization].
The troublesome symptoms of the seriously defective schizophrenics depend sometimes upon their unexpected sensitive experiences, which are not reported verbally and are guessed merely through the precise observations of the behaviour. By the treatment of the disturbances so found, the troublesome symptoms disappear. As an example of this "behaviour-analytical treatment" an old, defective schizophrenic with incontinence and negativism was introduced in this report, whose background suggested an intensive mysophobia, and was treated successfully. Some forsaken inmates of the asylums might be helped in this way.


Uricemia and homocysteinemia: nontraditional risk factors in the early stages of chronic kidney disease--preliminary data.
Patients with chronic kidney disease (CKD) show a risk of cardiovascular death, which is 10-100 times higher than that in the general population. This increase is not completely explained by the traditional cardiovascular risk factors. Hyperuricemia and hyperhomocysteinemia are highly prevalent in CKD. Patients suffering from these complications present accelerated atherosclerosis, determined mainly from the endothelial dysfunction that carries out a central role in the pathogenesis of cardiovascular diseases. The hypothesis was that brachial artery flow mediated dilation (FMD) and carotid intima-media thickness (cIMT) evaluation can be considered as early and systemic markers of atherosclerosis and that nontraditional risk factors, such as hyperhomocysteinemia and hyperuricemia, are associated with early endothelial dysfunction and vascular damage in patients suffering from first- and second-stage CKD. The study comprised 50 patients, 10 for each CKD stage, and 15 age- and sex-matched healthy controls. We compared the traditional and nontraditional factors for cardiovascular diseases with alterations of vascular reactivity, such as cIMT, and brachial artery FMD, in patients affected by CKD with those in the control group. In our study, hyperuricemia was significantly and independently associated with brachial artery FMD reduction (p = 0.007), while hyperhomocysteinemia was significantly and independently associated with carotid intima-media thickening (p = 0.021) in patients at Stage I and II KDOQI (Kidney Disease Outcomes Quality Initiative). In our study, we found a progressive increase in the inflammatory indices and endothelial dysfunction at the early stages of CKD. Hyperuricemia and hyperhomocysteinemia were associated with IMT and FMD at Stage I-III KDOQI, and can be used as markers of subclinical atherosclerosis, especially in nephropathic patients with high cardiovascular risk.


Frequent transient hepatitis C viremia without seroconversion among healthcare workers in Cairo, Egypt.
With 10% of the general population aged 15-59 years chronically infected with hepatitis C virus (HCV), Egypt is the country with the highest HCV prevalence worldwide. Healthcare workers (HCWs) are therefore at particularly high risk of HCV infection. Our aim was to study HCV infection risk after occupational blood exposure among HCWs in Cairo. The study was conducted in 2008-2010 at Ain Shams University Hospital, Cairo. HCWs reporting an occupational blood exposure at screening, having neither anti-HCV antibodies (anti-HCV) nor HCV RNA, and exposed to a HCV RNA positive patient, were enrolled in a 6-month prospective cohort with follow-up visits at weeks 2, 4, 8, 12 and 24. During follow-up, anti-HCV, HCV RNA and ALT were tested. Among 597 HCWs who reported a blood exposure, anti-HCV prevalence at screening was 7.2%, not different from that of the general population of Cairo after age-standardization (11.6% and 10.4% respectively, p = 0.62). The proportion of HCV viremia among index patients was 37%. Of 73 HCWs exposed to HCV RNA from index patients, nine (12.3%; 95%CI, 5.8-22.1%) presented transient viremia, the majority of which occurred within the first two weeks after exposure. None of the workers presented seroconversion or elevation of ALT. HCWs of a general University hospital in Cairo were exposed to a highly viremic patient population. They experienced frequent occupational blood exposures, particularly in early stages of training. These exposures resulted in transient viremic episodes without established infection. These findings call for further investigation of potential immune protection against HCV persistence in this high risk group.


Convalescent Plasma: Education and Administration Implications.
Convalescent plasma has emerged as a treatment that merits consideration for COVID-19-positive patients requiring hospitalization. With millions of cases of COVID-19 being reported worldwide, nurses across specialties are caring for infected patients and are often the primary patient educators about convalescent plasma treatment. Keeping abreast of current clinical guidelines and evidence-based practice allows nurses to identify patients who should be considered for treatment, understand the administration guidelines, and be aware of the toxicity profile to provide safe and high-quality care to patients. The purpose of this article is to provide information on convalescent plasma as a treatment for COVID-19.


Green fluorescent protein bone marrow cells express hematopoietic and neural antigens in culture and migrate within the neonatal rat brain.
Finding a reliable source of alternative neural stem cells for treatment of various diseases and injuries affecting the central nervous system is a challenge. Numerous studies have shown that hematopoietic and nonhematopoietic progenitors derived from bone marrow (BM) under specific conditions are able to differentiate into cells of all three germ layers. Recently, it was reported that cultured, unfractionated (whole) adult BM cells form nestin-positive spheres that can later initiate neural differentiation (Kabos et al., 2002). The identity of the subpopulation of BM cells that contributes to neural differentiation remains unknown. We therefore analyzed the hematopoietic and neural features of cultured, unfractionated BM cells derived from a transgenic mouse that expresses green fluorescent protein (GFP) in all tissues. We also transplanted the BM cells into the subventricular zone (SVZ), a region known to support postnatal neurogenesis. After injection of BM cells into the neurogenic SVZ in neonatal rats, we found surviving GFP+ BM cells close to the injection site and in various brain regions, including corpus callosum and subcortical white matter. Many of the grafted cells were detected within the rostral migratory stream (RMS), moving toward the olfactory bulb (OB), and some cells reached the subependymal zone of the OB. Our in vitro experiments revealed that murine GFP+ BM cells retained their proliferation and differentiation potential and predominantly preserved their hematopoietic identity (CD45, CD90, CD133), although a few expressed neural antigens (nestin, glial fibrillary acdiic protein, TuJ1).


Alveoli, teeth, and tooth loss: Understanding the homology of internal mandibular structures in mysticete cetaceans.
The evolution of filter feeding in baleen whales (Mysticeti) facilitated a wide range of ecological diversity and extreme gigantism. The innovation of filter feeding evolved in a shift from a mineralized upper and lower dentition in stem mysticetes to keratinous baleen plates that hang only from the roof of the mouth in extant species, which are all edentulous as adults. While all extant mysticetes are born with a mandible lacking a specialized feeding structure (i.e., baleen), the bony surface retains small foramina with elongated sulci that often merge together in what has been termed the alveolar gutter. Because mysticete embryos develop tooth buds that resorb in utero, these foramina have been interpreted as homologous to tooth alveoli in other mammals. Here, we test this homology by creating 3D models of the internal mandibular morphology from terrestrial artiodactyls and fossil and extant cetaceans, including stem cetaceans, odontocetes and mysticetes. We demonstrate that dorsal foramina on the mandible communicate with the mandibular canal via smaller canals, which we explain within the context of known mechanical models of bone resorption. We suggest that these dorsal foramina represent distinct branches of the inferior alveolar nerve (or artery), rather than alveoli homologous with those of other mammals. As a functional explanation, we propose that these branches provide sensation to the dorsal margin of the mandible to facilitate placement and occlusion of the baleen plates during filer feeding.


Synovial chondromatosis of the metacarpophalangeal joint: case report and review of the literature.
Intra-articular synovial chondromatosis in the hand is rare but should be considered in the differential diagnosis of a swollen, stiff or painful joint. Other possible diagnoses include osteoarthritis, rheumatoid arthritis, gout, trauma and chronic infection, and unless enchondral ossification of loose bodies is seen the diagnosis of synovial chondromatosis may not be made preoperatively. A 69-year-old man with synovial chondromatosis of the metacarpophalangeal joint is reported. The joint was swollen and tender. He had not sustained trauma and there was no evidence of arthritis, involvement of other joints or infection. Complete synovectomy with removal of all loose bodies was successful and his symptoms resolved. Intra-articular synovial chondromatosis is a benign condition, but spontaneous resolution is the exception and surgical synovectomy remains the most effective treatment.