[Influence of physical workload patterns and breaks on heart rate recovery].
It is necessary to try to achieve quick recovery from work strain by setting adequate breaks and shortening continuous working hours to prevent the accumulation of fatigue. However, there has been no research investigating the influence of the timing and lengths of breaks on individual aerobic capacities in recovery from work strain. In this study, we set three load patterns based on the length and timing of breaks: "no breaks", "one break" and "regular small breaks". We examined the differences of the heart rate variation in the recovery time after working considering the individual aerobic capacities (VO(2)max) of ten male subjects (mean age 22.3 +/- 1.7 yr) in the case of 50 W or 100 W workloads on a bicycle ergometer. When individual aerobic capacity was not considered, the "regular small breaks" condition led to the quickest recovery to the level of the resting heart rate at 50 W workload. Not all conditions showed heart rate recovery within 30 min at 100 W workload. On the other hand, when individual aerobic capacity was considered, the "regular small breaks" condition showed the quickest recovery to the level of the resting heart rate at 50 W workload in the low aerobic capacity group (VO(2)max mean 42.2 +/- 3.7 ml/kg/min). However, in the high aerobic capacity group (VO(2)max mean 54.5 +/- 4.1 ml/kg/min), the "regular small breaks" condition resulted in the quickest recovery of the level to the resting heart rate at 100W workload. Two-way repeated measures ANOVA was performed for the recovery time with respect to the rate of increase from resting heart rate to examine the influence on heart rate recovery of physical activity loads, workload patterns and individual fitness. Physical activity loads were strongly related to the increase from resting heart rate in recovery time, and workload patterns showed that the regular small breaks condition was related to the heart rate recovery in the high fitness subjects in the case of the exercise intensity of 100 W. The effect of work strain decreased by workload patterns was defined by the relationship between physical activity load and individual fitness. In future occupational health activities, it will be important to manage work in order to aim for quick recovery from work strain by using ergonomics. The evaluation of the level of the physical activity load and distribution of proper break times during working in addition to individual aerobic capacities are important in considerations of quick recovery from work strain.


Heterotopic Ossification Secondary to Gunshot and Fragment Wounds in a Golden Eagle ( Aquila chrysaetos ).
Heterotopic ossification is the process of pathologic bone formation in soft tissue structures that usually do not form bone. An immature golden eagle ( Aquila chrysaetos ) was examined 2 months after a gunshot wound in the right wing. A solid oval mass with a gun pellet at its core was found attached to the ulna by a bony pedicle and was surgically excised. Heterotopic ossification secondary to gunshot and fragment wounds in the right ulna was diagnosed based on clinical, radiographic, and histopathologic findings. This report is the first to describe heterotopic ossification occurring around a gun pellet in a bird.


Antibiofilm Activities of Biogenic Silver Nanoparticles Against Candida albicans.
Biofilms are microbial colonies that are encased in an organic polymeric matrix and are resistant to antimicrobial treatments. Biofilms can adhere to both biotic and abiotic surfaces, allowing them to colonize medical equipment such as urinary and intravenous catheters, mechanical heart valves, endotracheal tubes, and prosthetic joints. Candida albicans biofilm is the major etiological cause of the pathogenesis of candidiasis in which its unobstructed growth occurs in the oral cavity; trachea, and catheters that progress to systemic infections in the worst scenarios. There is an urgent need to discover novel biofilm preventive and curative agents. In the present investigation, an effort is made to observe the role of cyanobacteria-derived AgNPs as a new antibiofilm agent with special reference to candidiasis. AgNPs synthesized through the green route using Anabaena variabilis cell extract were characterized by UV-visible spectroscopy. The nanoparticles were spherical in shape with 11-15 nm size and were monodispersed. The minimum inhibitory concentration (MIC) of AgNPs was obtained at 12.5 μg/mL against C. albicans. AgNPs 25 μg/mL showed 79% fungal cell membrane permeability and 22.2% ROS production. AgNPs (25 μg/mL) also facilitated 62.5% of biofilm inhibition and degradation. Therefore, AgNPs could be considered as a promising antifungal agent to control biofilm produced by C. albicans.


Flip a coin: Collaborative consumption or Sharing Economy in Ophthalmology services.
The sharing economy and collaborative consumption provide new opportunities in health care, especially to physicians, medical organizations, and consumers (patients). In health care services, there has been a long debate on the implementation and the characteristics of such concepts. Both terms may be very cost-effective, if applied accordingly. The aim of this paper was to investigate whether the concepts of sharing economy and collaborative consumption can be successfully used in health care services, with a specific interest in Ophthalmology services. The conclusions reached revealed that sharing economy in Ophthalmology services should be used from a consumer perspective, whereas the collaborative consumption concept should be used from a provider's perspective.


Monocyte-derived human macrophages mediate anergy in allogeneic T cells and induce regulatory T cells.
Activation of alloreactive T cells by APCs such as dendritic cells (DC) has been implicated as crucial step in transplant rejection. In contrast, it has been proposed that macrophages (Mphi) maintain tolerance toward alloantigens. It was therefore the aim of this study to further analyze the T cell-stimulatory capacity of mature DC and Mphi in vitro using the model of allogeneic MLR. There was a strong proliferative response in T cells cocultured with DC, which was further increased upon restimulation in a secondary MLR. In contrast, T cells did not proliferate in cocultures with Mphi despite costimulation with anti-CD28 and IL-2. Cytokine analysis revealed considerable levels of IL-10 in cocultures of T cells with Mphi, whereas high amounts of IL-2 and IFN-gamma were present in cocultures with DC. There was only minimal T cell proliferation in a secondary MLR when T cells were rescued from primary MLR with Mphi and restimulated with DC of the same donor, or DC of an unrelated donor (third party), whereas a strong primary proliferative response was observed in resting T cells, demonstrating induction of T cell anergy by Mphi. Functional analysis of T cells rescued from cocultures with Mphi demonstrated that anergy was at least partly mediated by IL-10-producing regulatory T cells induced by Mphi. These results demonstrate that Mphi drive the differentiation of regulatory T cells and mediate anergy in allogeneic T cells, supporting the concept that Mphi maintain peripheral tolerance in vivo.


Indocyanine Green Lymphography for Evaluation of Breast Lymphedema Secondary to Breast Cancer Treatments.
Although breast lymphedema (BL) significantly deteriorates quality of life (QOL) of breast cancer survivors, little is known and pathophysiological severity staging system is yet reported. This study aimed to evaluate usefulness of a novel BL severity staging system based on indocyanine green (ICG) lymphography findings. Breast cancer survivors with breast symptoms who underwent breast ICG lymphography were included. Breast ICG lymphography stage was determined based on visibility of linear pattern and extension of dermal backflow patterns. Prevalence of breast symptoms and lymphedema QOL score (LeQOLiS) was compared according to the stage. Thirty-seven patients were included. Breast ICG lymphography stage included stage 0 in 11 (29.7%) cases, stage I in 3 (8.1%) cases, stage II in 11 (29.7%) cases, stage III in 6 (16.2%) cases, stage IV in 4 (10.8%) cases, and stage V in 2 (5.4%) cases. Higher ICG stages were associated with more frequent prevalence of breast swelling (p = 0.020), breast pain (p = 0.238), and breast cellulitis (p = 0.024), and with higher LeQOLiS (p < 0.001). ICG lymphography allows clear visualization of superficial lymph circulation in the breast. Higher breast ICG lymphography stages are associated with more frequent prevalence of BL-related symptoms and worse QOL.


Reticulated acanthoma with sebaceous differentiation: another sebaceous neoplasm associated with Muir-Torre syndrome?
Reticulated acanthoma with sebaceous differentiation (RASD) represents a rare benign cutaneous epithelial neoplasm with sebaceous differentiation. There has been much speculation about the relationship between RASD and Muir-Torre syndrome (MTS). We report a 53 year-old man who presented with RASD in addition to a prior history of sebaceous adenomas. Immunohistochemically, the tumour cells in the RASD and sebaceous adenomas showed a significantly reduced MSH6 protein expression, whereas there was no loss of MLH1, MSH2 and PMS2. This benign neoplasm, which can be mistaken for various other cutaneous lesions with sebaceous differentiation, deserves wider recognition for its possible association with MTS.


Bilateral Divergent Shoulder's Fracture Dislocation Case in an Ischemic Stroke Patient.
The literature review revealed that nowadays only about 15 cases of bilateral shoulder dislocation associated with the fracture of the upper end of the humerus have been published. The triad of lesional mechanism designated by the triple syndrome E composed of epilepsy, electrocution, and external trauma was the circumstances noted in which these fractures dislocations occur with migration of the two humeral heads either forward or backward. An architect of 36-year-old, right-handed, was admitted in emergency department for loss of knowledge of progressive installation. At admission the blood pressure, pulse, and temperature were normal. There was a right hemiparesis predominantly in brachiofacial side and an aphasia. After intensive resuscitation measures, the cerebral computed tomography scan revealed a left temporoparietal hypodensity area affecting the middle cerebral artery superficial territory with a mass effect compatible with acute ischemic stroke. During the hospitalization, episodes of generalized tonic-clonic convulsions appeared with a fever at 39°C and a leukocytosis at 35 thousand on the 5th day. These convulsions caused on the right shoulder an anterior dislocation under coracoid, associated with a fracture of the greater tubercle and on the left shoulder, posterior dislocation with much displaced comminuted articular proximal humeral fracture. We did reduction by external maneuvers for the right shoulder and open reduction with internal fixation by anatomical plate of left shoulder lesions. In the immediate aftermath of surgery, he presented episodes of agitation which led to the dismantling of the left shoulder fixation. He was evacuated to the North Country where an ablation of the left shoulder material and stabilization by locked plate were carried out. The sequelae were marked by the occurrence of an osteomyelitis with osteolysis of the entire upper right humerus extremity. It will require an inverted prosthesis. The surgical treatment must be done by a solid assembly and consultation with neurologists and anesthetists is essential. This multidisciplinary management could prevent any convulsive postoperative seizures that would risk sacrificing all therapeutic efforts.


[The effect of vascular risk factors in arteriopathy of the legs in women].
Here the analysis of the results of a multicentered prospective epidemiologic study that has counted only the new cases of chronic atherosclerosis obliterans of the lower extremities. Included have been 989 patients (659 men and 330 women). Critical analysis of data allows a comparative study between the sexes. Thus, specifics of arteriopathy among women can be drawn. It appears that they are only the consequences of the fact that men and women reflect a different level of tobacco use in the two populations.


Age- and disease-related decline in immune function: an opportunity for "thymus-boosting" therapies.
The thymus is the site of production of mature T lymphocytes and thus is indispensable for the development and maintenance of the T cell-mediated arm of the immune system. Thymic production of mature T cells is critically dependent on an influx of bone marrow-derived progenitor T cells that undergo replication and selection within the thymus. Thymus cellularity and thymic hormone secretion reach a peak during the first year of life and then decline gradually until the age of 50-60 years, a process known as "thymic involution." A rapid reduction of thymus cellularity occurs in young patients following injuries, chemotherapy, and other forms of stress. The mechanisms underlying the involution process appear to be dependent on factors intrinsic to the thymic tissue, such as the local production of cytokines and chemoattractants, promoting the recruitment, growth, and differentiation of bone marrow-derived T cell progenitors in the thymus, as well as extrinsic factors, such as systemic levels of endocrine hormones and mediators released by intrathymic nerves of the autonomic nervous system. Knowledge of these factors provides a rational basis for the development of an approach based on tissue engineering that could be used to provide either temporary or permanent reconstitution of thymic function.


Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics.
Understanding the role of the lipid bilayer in membrane protein structure and dynamics is needed for tertiary structure determination methods. However, the molecular details are not well understood. Molecular dynamics computer calculations can provide insight into these molecular details of protein:lipid interactions. This paper reports on 10 simulations of individual alpha-helices in explicit lipid bilayers. The 10 helices were selected from the bacteriorhodopsin structure as representative alpha-helical membrane folding components. The bilayer is constructed of dimyristoyl phosphatidylcholine molecules. The only major difference between simulations is the primary sequence of the alpha-helix. The results show dramatic differences in motional behavior between alpha-helices. For example, helix A has much smaller root-mean-squared deviations than does helix D. This can be understood in terms of the presence of aromatic residues at the interface for helix A that are not present in helix D. Additional motions are possible for the helices that contain proline side chains relative to other amino acids. The results thus provide insight into the types of motion and the average structures possible for helices within the bilayer setting and demonstrate the strength of molecular simulations in providing molecular details that are not directly visualized in experiments.


[Choice of the anesthesia method during performance of reconstructive operation on aorta and main vessels of the lower extremities in patients with concurrent hypertonic and ischemic diseases of the heart].
The results of comparative analysis of hemodynamic changes in patients of both groups with hypertonic and ischemic diseases of the heart were expounded. In these patients there were applied different methods of anesthesia during performance of reconstructive operation on aorta and vessels of lower extremities: in 66 of them (1 group) operation was performed in condition of endotracheal narcosis with neuroleptanalgesia, in 56 (2 group)--the prolonged epidural anesthesia. Stability of hemodynamics in perioperative period and lesser frequency of surgical and cardiological complications had allowed to recommend epidural anesthesia during performance of such operations.


[Effect of recombinant Sp1 gene on the collagen expression of hypertrophic scar fibroblasts in vitro].
To explore the feasibility of transfecting recombinant Sp1 into hypertrophic scar fibroblasts and investigate the proliferation and collagen I, III synthesis in the transfected cells. Recombinant human Sp1 was transfected into hypertrophic scar fibroblasts with the karyocyte expressive vector. The expression of Sp1, collagen I, III mRNA was tested by real time PCR. The change of cell proliferation was observed with CCK8 colorimeter. About 30% of transfected hypertrophic scar fibroblasts showed green fluorescence positive. The relative expression of Sp1 mRNA in transfected cells, empty-vector cell or untransfected cells group was 5.26 +/- 0.76, 1.08 +/- 0.18, 1.09 +/- 0.15, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P <0.01, n = 5). Expression of collagen I, III mRNA was 2.49 +/- 0.40 and 1.88 +/- 0.30 in transfected cells, 0.96 +/- 0.18 and 0.95 +/- 0.18 in empty-vector cell, and 0.97 +/- 0.15 and 0.93 +/- 0.13 in untransfected cells, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P < 0.01, n = 5). The hypertrophic scar fibroblasts could be as the target cells of Sp1 gene transfection. Sp1 gene may play an important role in abnormal collagen metabolism in hypertrophic scar.


Optimal inter-stimulus interval for paired associative stimulation with mechanical stimulation.
In this paper, inter-stimulus interval (ISI) of paired associative stimulation (PAS) with mechanical stimulation was analyzed. PAS is a prominent therapeutic intervention for individuals after stroke and helps to improve limb function by strengthening excitatory synapses and inducing neural plasticity. This intervention involves repeated application of transcranial magnetic stimulation (TMS) followed by peripheral stimulation. When responses to both stimulations are overlapped in the brain at the same time, this successful PAS is expected to induce long term potentiation (LTP) which leads to a neural plasticity phenomenon. Therefore ISI between these two stimulations is very crucial in this treatment. Instead of electrical stimulation in general PAS, mechanical stimulation was used in this study due to some promising aspects of mechanical stimulation. Long latency stretch response (LLSR) was observed in electromyography (EMG) during the PAS with mechanical stimulation, since LLSR reflects successful overlapping of two stimulations. Each subject had specific range of ISIs, or a time window, that leads to successful overlapping of paired stimulations. These time window lengths varied between 5ms and 105 ms, and within this range it can be guaranteed to obtain LLSR in EMG at least 40% among the all PAS trials. In addition, normally distributed responses within time window suggests that the optimal ISI which results in the highest number of LLSRs is the average of the time window. This result suggests that PAS with mechanical stimulation could lead to a rehabilitation effect by regaining motor functionality when the two stimulations are paired with the optimal ISI and it could provide a significant advancement in neuromodulation.


Model study of the enzymatic modification of natural extracts: peroxidase-based removal of eugenol from rose essential oil.
A protocol based on the use of horseradish peroxidase (HRP) is proposed for the removal of allergenic eugenol from rose essential oil without loss of the organoleptic quality and with a good conservation of the chemical composition. For the first time, an enzyme-based strategy is proposed for essential oils treatment and opens new opportunities in the detoxification of natural extracts used in perfumery and cosmetics. Our results on eugenol in rose essential oil constitute a first step toward the development of efficient and mild processes for the removal of more toxic compounds of natural extracts.


Orally administered beta-lactamase enzymes represent a novel strategy to prevent colonization by Clostridium difficile.
Antibiotics that are excreted into the intestinal tract and that disrupt the indigenous microbiota may promote infection by Clostridium difficile. We previously demonstrated that oral administration of a proteolysis-resistant, recombinant class A beta-lactamase inactivates ampicillin or piperacillin excreted into the small intestine during parenteral treatment. We hypothesized that oral administration of this beta-lactamase in conjunction with parenteral ampicillin or piperacillin would preserve the colonic microbiota, thus preventing the overgrowth of and toxin production by C. difficile in mice. Subcutaneous ampicillin, subcutaneous piperacillin or either of these plus oral beta-lactamase or either of these plus tazobactam-inactivated oral beta-lactamase were administered to mice 24 and 12 h prior to harvest of caecal contents. Contents were inoculated with one of four strains of C. difficile, and growth and toxin production were assessed after 24 h of incubation under anaerobic conditions. To assess changes in stool microbiota, denaturing gradient gel electrophoresis (DGGE) of PCR-amplified ribosomal RNA genes was performed. Mice treated with ampicillin, piperacillin or either of these plus tazobactam-inactivated oral beta-lactamase developed high-density colonization with C. difficile, whereas those treated with ampicillin or piperacillin plus the beta-lactamase did not. DGGE demonstrated that antibiotic treatment resulted in significant alteration of the indigenous stool microbiota, whereas antibiotic plus beta-lactamase treatment did not. Administration of oral recombinant beta-lactamase preserved the colonic microbiota of mice during parenteral beta-lactam antibiotic treatment and prevented the overgrowth of and toxin production by C. difficile in caecal contents. Oral beta-lactamase therapy may represent a novel approach towards preventing C. difficile infections in healthcare settings.


Renal cyst pseudoenhancement with beam hardening effect on CT attenuation.
The purpose of this study was to evaluate the extent of pseudoenhancement in a phantom model using three different CT scanners. The phantom consisted of a water-filled balloon (cyst) suspended in varying concentrations of iodine solution, meant to simulate varying levels of renal enhancement. The phantom was scanned with single detector-row CT scanners of three different manufacturers. All scans were performed at 120 kV and 200 mA with 5 mm collimation. The degree of pseudoenhancement differed among the three scanners. In two of the scanners, the attenuation of water in the balloon (cyst) was noted to increase significantly as the iodine concentration in the cylinder was increased. However, the degree of pseudoenhancement was different between the two scanners. In the other scanner, attenuation of the cyst was noted to decrease as the iodine concentration in the cylinder decreased and to increase as the iodine concentration in the cylinder increased. The degree of pseudoenhancement may vary in scanners of different manufacturers. We may need to check the pattern and degree of pseudoenhancement in CT scanners before determining the enhancement threshold for simple renal cyst.


Regulator of G protein signalling 16 is a target for a porcine circovirus type 2 protein.
Interaction studies have suggested that the non-structural protein encoded by open reading frame 3 (ORF3) of porcine circovirus type 2 (PCV2) binds specifically to a regulator of G protein signalling (RGS) related to human RGS16 (huRGS16). The full-length clone of RGS16 was generated from porcine cells and sequence analysis revealed a close relationship to huRGS16 and murine RGS16. In vitro pull-down experiments verified an interaction between porcine RGS16 (poRGS16) and ORF3 from PCV2. Using GST-linked ORF3 proteins from three different genogroups of PCV2 and from porcine circovirus type 1 (PCV1) in the pull-down experiments indicated that there were differences in their ability to bind poRGS16. Quantitative RT-PCR demonstrated that the expression of poRGS16 mRNA could be induced by a number of cell activators including mitogens (LPS and PHA), interferon inducers (ODN 2216 and poly I : C) and the neurotransmitter norepinephrine. Immunofluorescence labelling confirmed the induced expression of poRGS16 at the protein level and suggested that the PCV2 ORF3 protein co-localized with poRGS16 in LPS-activated porcine PBMC. Furthermore, poRGS16 appeared to participate in the translocation of the ORF3 protein into the cell nucleus, suggesting that the observed interaction may play an important role in the infection biology of porcine circovirus.


Monitoring of Microphysiological Systems: Integrating Sensors and Real-Time Data Analysis toward Autonomous Decision-Making.
Microphysiological systems replicate human organ function and are promising technologies for discovery of translatable biomarkers, pharmaceuticals, and regenerative therapies. Because microphysiological systems require complex microscale anatomical structures and heterogeneous cell populations, a major challenge remains to manufacture and operate these products with reproducible and standardized function. In this Perspective, three stages of microphysiological system monitoring, including process, development, and function, are assessed. The unique features and remaining technical challenges for the required sensors are discussed. Monitoring of microphysiological systems requires nondestructive, continuous biosensors and imaging techniques. With such tools, the extent of cellular and tissue development, as well as function, can be autonomously determined and optimized by correlating physical and chemical sensor outputs with markers of physiological performance. Ultimately, data fusion and analyses across process, development, and function monitors can be implemented to adopt microphysiological systems for broad research and commercial applications.


The effectiveness of ergonomics interventions in reducing upper limb work-related musculoskeletal pain and dysfunction in sonographers, surgeons and dentists: a systematic review.
The aim of this systematic review was to summarise the effects of ergonomics interventions on work-related upper limb musculoskeletal pain and dysfunction, and on productivity in sonographers, surgeons and dentists. A total of 31 studies were included. All studies reported effects on upper limb pain. Nine studies reported effects on dysfunction and only two studies reported effects on productivity. Moderately strong evidence in reducing upper limb pain was found for instigation of microbreaks into long duration surgical procedures, and the use of wider, lighter handles in dental instruments. Moderate evidence was also found for use of prismatic glasses and favourable positioning in reducing upper limb pain. Weak, inconsistent or no evidence was found for all other ergonomics interventions in reducing upper limb pain and dysfunction and increasing productivity. The lack of high quality research, particularly in sonographers and in the outcome of productivity, should be addressed. Practitioner summary: This systematic review investigates the effectiveness of ergonomics interventions on upper limb pain, dysfunction and productivity in sonographers, dentists and surgeons. Instigation of microbreaks during long duration procedures and the use of wider, lighter instrument handles were most effective in reducing upper limb work-related pain. Abbreviations: ANOVA: analysis of variance; CLS: conventional laparoscopic surgery; DMAIC: define, measure, analyze, improve and control; GRADE: grading of recommendations, assessment, development and evaluations; HD: high definition; PRISMA: preferred reporting items for systematic reviews and meta-analyses; PROSPERO: The International Prospective Register of Systematic Reviews; RCT: randomised control trial; SILS: single incision laparoscopic surgery; VITOM: video telescopic operative microscope; WNSWLHD: Western New South Wales Local Health District; WMSD: work related musculoskeletal disorder.


Mapping brain activity on the verge of a photically induced generalized tonic-clonic seizure.
In a photosensitive patient intermittent photic stimulation (IPS) accidentally provoked a generalized tonic-clonic seizure during simultaneous recordings of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Before seizure onset, IPS consistently induced generalized photoparoxysmal responses (PPRs). These PPRs were associated with increases in blood oxygen level dependent (BOLD) signal in the visual cortex, the thalamus, and both superior colliculi, and a decrease in BOLD signal in the frontoparietal areas. The BOLD signal in the visual cortex increased in magnitude during consecutive epochs of IPS associated with PPRs. We propose that repeated IPS led to an excessive amount of neuronal activity in the visual cortex that evoked PPRs and finally exceeded a critical threshold and triggered a generalized seizure.


Exogenous spermine attenuates diabetic kidney injury in rats by inhibiting AMPK/mTOR signaling pathway.
Diabetic nephropathy (DN) is the primary cause of end‑stage renal disease, which is closely associated with dysfunction of the podocytes, the main component of the glomerular filtration membrane; however, the exact underlying mechanism is unknown. Polyamines, including spermine, spermidine and putrescine, have antioxidant and anti‑aging properties that are involved in the progression of numerous diseases, but their role in DN has not yet been reported. The present study aimed to explore the role of polyamines in DN, particularly in podocyte injury, and to reveal the molecular mechanism underlying the protective effect of exogenous spermine. Streptozotocin intraperitoneal injection‑induced type 1 diabetic (T1D) rat models and high glucose (HG)‑stimulated podocyte injury models were established. It was found that in T1D rat kidneys and HG‑induced podocytes, ornithine decarboxylase (a key enzyme for polyamine synthesis) was downregulated, while spermidine/spermine N1‑acetyltransferase (a key enzyme for polyamines degradation) was upregulated, which suggested that reduction of the polyamine metabolic pool particularly decreased spermine content, is a major factor in DN progression. In addition, hyperglycemia can induce an increased rat kidney weight ratio, serum creatinine, urea, urinary albumin excretion and glomerular cell matrix levels, and promote mesangial thickening and loss or fusion of podocytes. The expression levels of podocyte marker proteins (nephrin, CD2‑associated protein and podocin) and autophagy‑related proteins [autophagy protein 5, microtube‑associated proteins 1A/1B light chain 3 (LC3)II/LC3I, Beclin 1 and phosphorylated (p)‑AMPK] were downregulated, while cleaved caspase‑3, P62 and p‑mTOR were increased. These changes could be improved by pretreatment with exogenous spermine or rapamycin (autophagic agonist). In conclusion, spermine may have the potential to prevent diabetic kidney injury in rats by promoting autophagy via regulating the AMPK/mTOR signaling pathway.


Ethnicity and changing functional health in middle and late life: a person-centered approach.
Following a person-centered approach, this research aims to depict distinct courses of disability and to ascertain how the probabilities of experiencing these trajectories vary across Black, Hispanic, and White middle-aged and older Americans. Data came from the 1995-2006 Health and Retirement Study, which involved a national sample of 18,486 Americans older than 50 years of age. Group-based semiparametric mixture models (Proc Traj) were used for data analysis. Five trajectories were identified: (a) excellent functional health (61%), (b) good functional health with small increasing disability (25%), (c) accelerated increase in disability (7%), (d) high but stable disability (4%), and (e) persistent severe impairment (3%). However, when time-varying covariates (e.g., martial status and health conditions) were controlled, only 3 trajectories emerged: (a) healthy functioning (53%), moderate functional decrement (40%), and (c) large functional decrement (8%). Black and Hispanic Americans had significantly higher probabilities than White Americans in experiencing poor functional health trajectories, with Blacks at greater risks than Hispanics. Parallel to the concepts of successful aging, usual aging, and pathological aging, there exist distinct courses of changing functional health over time. The mechanisms underlying changes in disability may vary between Black and Hispanic Americans.


[Does synaptic elimination contribute to the organization of cerebellar microzones of climbing fiber projection?].
In adult rats whose cerebellar Purkinje cells (PCs) remain polyinnervated by olivary climbing fibres (CFs) after postnatal irradiation, topographical maps of responsive PCs to mechanical stimulation of the third row of contralateral vibrissae show that these cells are more numerous and more diffusely distributed than in the normal rat. PCs responding with the "best responses" are distributed evenly from the midline to 400 microns lateral in the contralateral hemivermis of lobule VII, and not in a parasagittal microzone centred on the plane 200 microns as in the normal rat. Thus it seems likely that synaptic elimination should contribute to microzone formation during postnatal development of the normal cerebellum.


First-line everolimus and cisplatin in patients with advanced extrapulmonary neuroendocrine carcinoma: a nationwide phase 2 single-arm clinical trial.
Extrapulmonary neuroendocrine carcinoma (EP-NEC) are an aggressive subgroup of neuroendocrine neoplasms (NEN). Advanced EP-NEC is generally treated with platinum-based cytotoxic regimens, but progressive disease occurs rapidly, resulting in a poor prognosis. Genetic alterations in the mammalian target for rapamycin (mTOR) pathway have been identified in NEN, providing a rationale for treatment with the mTOR-inhibitor everolimus. A prospective phase 2 single-arm study included patients with advanced EP-NEC from three Dutch NEN expertise centres between March 2016 and January 2020. Treatment consisted of cisplatin 75 mg/m2 every 3 weeks in combination with daily everolimus 7.5 mg for a maximum of six cycles, followed by maintenance everolimus until disease progression. Primary endpoint was disease control rate (DCR), defined as the sum of overall response rate (ORR) plus the rate of stable disease according to RECIST 1.1, assessed at 9-week intervals. Toxicity was evaluated according to CTCAE version 5.0. Thirty-nine patients, with a median age of 64 years (range: 28-74), of whom 20 (51%) were male, were enrolled. DCR was 82.1% (95% confidence interval (CI): 66.4-92.4), with an ORR of 58.9% (CI: 42.1-74.4). Median duration of response was 6.4 (CI: 5.8-7.0) months and median progression-free survival was 6.0 (CI: 4.3-7.8) months. Three patients (8%) had durable responses lasting > 12 months. Median overall survival was 8.7 (CI: 7.8-9.6) months. Most common grade 3/4 toxicities were haematological (36%) and renal (21%). Everolimus in combination with cisplatin is an effective first-line treatment option for advanced EP-NEC, especially in highly selected patients. Clinicaltrials.gov, NCT02695459, https://clinicaltrials.gov/ct2/show/NCT02695459.


Expressed Breast Milk Analysis: Role of Individualized Protein Fortification to Avoid Protein Deficit After Preterm Birth and Improve Infant Outcomes.
Background: Expressed breast milk (EBM) protein content is highly variable between mothers and often below published values that are still used for EBM protein fortification strategies. This approach may result in significant protein deficit and suboptimal protein energy (P/E) ratio. The study aim was to determine whether individualized EBM protein analysis and fortification will reduce preterm infant protein deficits and improve growth and neurodevelopmental outcome. Study Methods: In a single-center randomized, blinded study of infants born at 24 0/7-29 6/7 weeks, mother-specific protein values measured by a milk analyzer were used to individualize infant-specific protein intake (interventional group, IG), and compared this to a standardized protein fortification scheme based on published values of EBM protein content of 1.4 g/dL (control group, CG). For IG, milk analyzer protein values of mother's EBM were used to adjust protein content of the EBM. The CG EBM protein content was adjusted using the standard published value of 1.4 g/dL and not based on milk analyzer values. EBM protein content, protein intake, protein/energy (P/E) ratio, weight (WT), head circumference (HC), length (L), growth velocity (GV) from 2 to 6 weeks of age, WT, HC and L Z-Scores at 32- and 35-weeks PMA, and lean body mass (35 weeks PMA skin fold thickness) were measured. Neurodevelopment was assessed by Bayley III at average 24 months corrected gestational age (CGA). Results: EBM protein content before fortification was significantly below published values of 1.4 g/dL at all time points in both CG and IG. CG protein deficit was significantly decreased and progressively worsened throughout the study. Individualized protein fortification in IG avoided protein deficit and optimized P/E ratio. Although no significant change in short-term GV (at 6 weeks of age) was seen between groups, IG infants born at <27 weeks had significant improvements in WT and L z-scores, and leaner body mass at 32 and 35 weeks PMA. IG exhibited significantly improved cognitive scores at 24 months CGA. Conclusions: Infant-specific protein supplementation of mother's EBM optimized P/E ratio by eliminating protein deficit and improved growth z scores at 32- and 35-weeks PMA and neurocognitive testing at 24 months.


The current state of affairs for disaster planning for a nuclear terrorist attack.
The author presents current thinking on the effects of an atomic bomb blast from a medical point of view and will argue that current US Federal plans for a nuclear disaster are simply crude, insufficient, disarticulated, and principally relies on martial law as a means of crowd control. The simple physics of a fusion reaction bomb is discussed along with the plans of other countries, apparently "secret"American plans, which show a poor knowledge of the physics of nuclear bombs as well as poor insight into what will be needed to help the maximum number of citizens. An alternative plan involving computer modeling and educating the public to the effects of a fission explosion are presented. The key issue of statewide planning is discussed, as the Federal government has dumped medical problems on "the local level."


Recent advances in IOL surgery.
Tremendous progress is made in recent time in the field of Ophthalmology especially after advent of IOL implantation surgery. Recent advance in anaesthesia/IOL, designs/IOL, quotings/cantering, techniques/advances in operating microscope and advances in suture materials/needles etc. will be discussed.


Comparison of Massage and Prone Position on Heart Rate and Blood Oxygen Saturation Level in Preterm Neonates Hospitalized in Neonatal Intensive Care Unit: A Randomized Controlled Trial.
These days, most of the admitted infants in neonatal intensive care units (NICU) are premature infants. Infant massage and prone position has been recommended for several decades to have a positive effect on preterm and low birth weight infants. The objective of this study was to determine the effects of neonatal massage with prone positioning in preterm infants on Heart Rate (HR), and Oxygen Saturation (O2Sa) status. This is a controlled randomized three-group clinical trial study conducted on hospitalized infants in selected hospitals of Alborz University of Medical Sciences in Karaj-Iran. There are about 75 preterm infants (33-37 weeks) who met inclusion criteria were randomly assigned to groups of position, massage as intervention groups, and a control group. Intervention (prone position and massage) was administrated for five straight days. The repeated measure ANOVA test was performed to evaluate and compare the effect of interventions. p value less than 0.05 was considered as statistical significance. The Repeated Measure two-way Analysis of Variance (RM-ANOVA) result showed a significant difference in HR and SaO2 in different time points among control, position and massage groups with RM-ANOVA (F 10,360 = 10.376, p < 0.001). HR values was reduced and SaO2 values was increased in intervention groups with RM-ANOVA (F 5,360 = 2.323, p < 0.001). Results showed that massage and prone position equally led to the reduction of HR and increase of SaO2, compared to control group.


Payer shifting after expansions in access to private care among veterans.
To investigate whether expanded access to Veterans Affairs (VA)-purchased care increased overall utilization or induced a shift from other payers to VA for emergency care among VA enrollees. This study included all emergency department (ED) encounters in 2019 from hospitals in the state of New York. We conducted a difference-in-differences analysis comparing VA enrollees to the general population before and after the implementation of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act in June 2019. We included all ED visits with individuals aged 30 or older at the time of the encounter. Individuals were considered eligible for the policy change if they were enrolled with VA at the beginning of 2019. Of the 5,577,199 ED visits in the sample, 4.9% (n = 253,799) were made by VA enrollees. Of these, 44.9% of visits were paid by Medicare, 32.8% occurred in VA facilities, and 7% were paid by private health insurance. There was a 6.4% (2.91 percentage points; std. error = 0.18; p < 0.01) decrease in the proportion of ED visits paid by Medicare among VA enrollees relative to the general population after the implementation of the MISSION Act in June 2019. This decrease was larger for ED visits with a subsequent inpatient admission (-8.4%; 4.87 percentage points; std. error = 0.33; p < 0.01). There was no statistically significant change in the total volume of ED visits (0.06%; std. error = 0.08; p = 0.45). Leveraging a novel dataset, we demonstrate that MISSION Act implementation coincided with a shift in the financing of non-VA ED visits from Medicare to VA without any increase in overall ED utilization. These findings have important implications for VA health care financing and delivery.


The Molecular Chaperone DNAJB6, but Not DNAJB1, Suppresses the Seeded Aggregation of Alpha-Synuclein in Cells.
Alpha-synuclein (α-Syn) can misfold and aggregate, causing the degeneration of dopaminergic neurons, as seen in Parkinson's disease (PD). We recently demonstrated that DNAJB6, a co-chaperone found in Lewy bodies (LB), suppresses the aggregation of α-Syn in cells and in vitro. In this study, we compared the capacities of DNAJB1 and DNAJB6 to suppress the seeded α-Syn aggregation in HEK293 cells expressing α-Syn tagged with cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP). The aggregation of α-Syn was seeded by the transfection of the cells with recombinant α-Syn pre-formed fibrils (PFFs), following the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated knockout (KO) of these two genes, respectively. We quantified the α-Syn aggregation by fluorescence microscopy and fluorescence resonance energy transfer (FRET) analysis. We detected significantly more aggregates in the DNAJB6 KO cells compared with the parental cells, whereas the DNAJB1 KO had no effect on the α-Syn aggregation. This is the first evidence that DNAJB6 can suppress α-Syn aggregation, induced by exogenous α-Syn seeds, in cells. Next, we explored whether this mechanism could be dependent on protein degradation pathways. We observed that the increase in the α-Syn PFF-induced aggregation in the DNAJB6 KO cells compared with the parental cells was strongly diminished upon the incubation of the cells with the proteasomal inhibitor MG132. These results consolidate that DNAJB6 is a suppressor of α-Syn aggregation, and suggest that DNAJB6 may target misfolded and/or aggregated α-Syn for proteasomal degradation.


Passive Control of Silane Diffusion for Gradient Application of Surface Properties.
Liquid lithography represents a robust technique for fabricating three-dimensional (3D) microstructures on a two-dimensional template. Silanization of a surface is often a key step in the liquid lithography process and is used to alter the surface energy of the substrate and, consequently, the shape of the 3D microfeatures produced. In this work, we present a passive technique that allows for the generation of silane gradients along the length of a substrate. The technique relies on a secondary diffusion chamber with a single opening, leading to a directional introduction of silane to the substrate via passive diffusion. The secondary chamber geometry influences the deposited gradient, which is shown to be well captured by Monte Carlo simulations that incorporate the passive diffusion and grafting processes. The technique ultimately allows the user to generate a range of substrate wettabilities on a single chip, enhancing throughput for organ-on-a-chip applications by mimicking the spatial variability of tissue topographies present in vivo.


Medical line entanglement: The unspoken patient safety hazard of medical devices.
In February 2022, the US Food and Drug Administration published a safety communication regarding the risk of strangulation from enteral feeding delivery sets. When it comes to the causes of accidental strangulation or asphyxiation, it is common knowledge that household items, such as window blind cords, are potential hazards. However, many people may not expect that medical devices may pose similar risks because of medical line entanglement (MLE). A survey of clinicians from pediatric acute care and outpatient facilities and caregivers of patients with medical lines was conducted with a goal to understand if clinicians and caregivers are aware of MLE, if healthcare facilities have policies and procedures related to the prevention of MLE, and if education about the risks of MLE is provided to caregivers when they first receive a medical device. The survey was shared through clinician organizations and patient advocacy groups. Responses were received from 191 clinicians and 117 caregivers. A majority of clinicians reported awareness of the risk of entanglement; however, few received direction from their employer on managing these risks. Caregivers (N = 106) reported that their child had experienced MLE, however only 9% of those caregivers recalled receiving any education on MLE from their healthcare providers. This survey demonstrates the need for healthcare facilities to develop programs for managing risks of MLE and for healthcare teams and caregivers to discuss prevention methods whenever an at-risk patient is sent home with a medical device that poses a risk for entanglement.


A cyanide-bridged Fe(II)-Nd(III) bimetallic assembly with a one-dimensional ladder-like chain structure.
The title complex, catena-poly[[[(2,2'-bipyridine-1kappa(2)N,N')tris(methanol-2kappaO)(nitrato-2kappa(2)O,O')-mu-cyanido-1:2C:N-cyanido-1kappaC-iron(II)neodymium(III)]-di-mu-cyanido-1:2'C:N;2:1'N:C] methanol solvate], {[Fe(II)Nd(III)(CN)(4)(NO(3))(C(10)H(8)N(2))(CH(3)OH)(3)].CH(3)OH}(n), is made up of ladder-like one-dimensional chains oriented along the c axis. Each ladder consists of two strands based on alternating Fe(II) and Nd(III) centers connected by cyanide bridges. Furthermore, two such parallel chains are connected by additional cyanide cross-pieces (the ;rungs' of the ladder), which likewise connect Fe(II) and Nd(III) centers, such that each [Fe(CN)(4)(bipy)](2-) unit (bipy is 2,2'-bipyridine) coordinates with three Nd(III) centers and each Nd(III) center connects with three different [Fe(CN)(4)(bipy)](2-) units. In the complex, the iron(II) cation is six-coordinated with a distorted octahedral geometry and the neodymium(III) cation is eight-coordinated with a distorted dodecahedral environment.


The needling technique and clinical application of point Zhibian.
Point Zhibian (BL 54) is often used for treatment of lumbago and scelalgia, flaccidity and arthralgia of the lower limb, constipation and dysuria, and hemorrhoid. As for the needling, the direction of the needle tip may vary, generally in three directions: 1) along the channel itself, 2) pointing to the genitals, and 3) pointing to the anus, the purpose of which is "leading qi to the diseased area" so as to obtain "effectiveness upon the arrival of qi". This point can also be used in combination with moxa stick, cupping, and point injection according to the individual conditions. However, only by differential application, can this point produce better therapeutic effects.


Evaluation of microvascularization in focal salivary gland lesions by contrast-enhanced ultrasonography (CEUS) and Color Doppler sonography.
To evaluate the dynamic microvascularization of focal salivary gland lesions by contrast-enhanced ultrasound (CEUS) and Color Doppler sonography. One hundred and sixty-eight patients with 183 major salivary gland lesions (mean age, 56 years; age range, 12-83 years) underwent gray-scale ultrasonography (US), Color Doppler (CD) and CEUS. The CD and CEUS patterns were classified into three types (scores 0-3). Combined score grades were calculated based on the CD and CEUS pattern scores. The time-intensity curve (TIC) parameters of CEUS were then analyzed. Sensitivity, specificity, negative predictive value and positive predictive value of combined score grades were also calculated. Among all the lesions, there were 161 in parotid gland, 22 in submandibular gland and 157 lesions were benign and 26 were malignant. For score grades (combined CEUS patterns with CD types), scores 1-2 were graded as benign; scores 3-4 were graded as indetermination-suspicious benign or malignant and scores 5-6 were graded as malignant.score 5-6 and score 1-2 indicated 24 (92.3%) and 135 (85.9%) malignant and benign lesions confirmed pathologically, respectively. The sensitivity and negative predicted value of combined score grades for malignant lesions were 92.3% and 98.5%, respectively. In addition, TIC analysis indicates that PI and AUC in malignant lesions were higher than those in benign lesions (p = 0.04 and 0.02, respectively). The combined score grade could be a useful method to assess the macro-and micro-vascularization and to differentiated diagnose benign and malignant lesions in major salivary glands.


[Evolution of resected bronchogenic carcinoma: 5-year survival. Our experience].
To review the causes of non-small cell bronchogenic carcinoma treated surgically with the intention to cure, in order to determine and analyze the course of disease in our patients, particularly regarding survival after five years, and to compare our outcomes with those reported in the literature. Retrospective study of all patients resected in our unit from September 1984 through December 1990. We also analyze sex, age, and course of disease over a period of 60 months, emphasizing surgically related mortality, TNM stage, type of resection and tissue type. We calculated five year actuarial survival globally and for each variable studied, excluding patients who died as a result of surgery and those who were lost to follow-up. We identified 115 cases (13.62% of all patients under-going surgery during this period). Nine patients (7.82%) died after surgery. Six patients were lost to follow-up and for three patients data were incomplete. Fifty-three patients died within five years of surgery. Forty-four lived at least five years. Overall actuarial survival was 56.05%. Analyzing by TNM stages, 54.9% were stage I, 50% were stage II and 32.09% were stage IIIa. Pneumonectomy was performed on 43.59%, single or double lobectomy on 50.29%, and infralobar resection on 33.33% Histology revealed 54.56% to be epidermoid versus 33.01% for all other tissue types. The outcomes for bronchogenic carcinomas resected in our department are comparable to those in the literature, survival after five postoperative years being similar to the rate reported for other series.


Characterizing the Pharmacokinetics and Biodistribution of Therapeutic Proteins: An Industry White Paper.
Characterization of the pharmacokinetics and biodistribution of therapeutic proteins (TPs) is a hot topic within the pharmaceutical industry, particularly with an ever-increasing catalog of novel modality TPs. Here, we review the current practices, and provide a summary of extensive cross-company discussions as well as a survey completed by International Consortium for Innovation and Quality members on this theme. A wide variety of in vitro, in vivo and in silico techniques are currently used to assess pharmacokinetics and biodistribution of TPs, and we discuss the relevance of these from an industry perspective, focusing on pharmacokinetic/pharmacodynamic understanding at the preclinical stage of development, and translation to human. We consider that the 'traditional in vivo biodistribution study' is becoming insufficient as a standalone tool, and thorough characterization of the interaction of the TP with its target(s), target biology, and off-target interactions at a microscopic scale are key to understand the overall biodistribution on a full-body scale. Our summary of the current challenges and our recommendations to address these issues could provide insight into the implementation of best practices in this area of drug development, and continued cross-company collaboration will be of tremendous value. SIGNIFICANCE STATEMENT: The Innovation and Quality Consortium Translational and ADME Sciences Leadership Group working group for the absorption, distribution, metabolism, and excretion of therapeutic proteins evaluates the current practices and challenges in characterizing the pharmacokinetics and biodistribution of therapeutic proteins during drug development, and proposes recommendations to address these issues. Incorporating the in vitro, in vivo and in silico approaches discussed herein may provide a pragmatic framework to increase early understanding of pharmacokinetic/pharmacodynamic relationships, and aid translational modeling for first-in-human dose predictions.


Bacteria in blood smears: overwhelming sepsis or trivial contamination.
It is unusual to find microorganisms in peripheral blood smears, and their presence is frequently associated with overwhelming sepsis and consequently a poor prognosis. In this report, we demonstrate 4 cases with bacteria in blood smears. Two of them had a fatal outcome, but the other 2 were caused by a contamination either via the central venous catheter or in vitro, both without dramatic outcome. The finding of bacteria in blood smears has to be interpreted carefully, and thorough examination of peripheral blood smears may be of great importance in the early diagnosis of bacteremia; however, in vitro contamination must be excluded.


Mining the Biomarkers and Associated-Drugs for Esophageal Squamous Cell Carcinoma by Bioinformatic Methods.
Esophageal squamous cell carcinoma (ESCC) showed limited treatment outcome and poor prognosis. This study aimed to screen potential biomarkers and drugs in ESCC. Firstly, GSE26886, GSE111044 and GSE77861 were downloaded from the Gene Expression Omnibus (GEO) database. Next, the differentially expressed genes (DEGs) between cancer and noncancerous tissues were analyzed by the GEO2R. The Gene Ontology (GO) annotation, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, the protein-protein interaction (PPI) analysis and hub genes screened were conducted by some bioinformatic methods, respectively. Lastly, the hub genes and potential drugs were verified by the GEPIA2 and the QuartataWeb database. The results showed that 13 up-regulated genes and 81 down-regulated genes were identified. In GO terms, DEGs were mainly associated with cell proliferation, cell migration and cell differentiation. DEGs did not cluster into the KEGG pathway. After hub genes validated, nine genes (FLG, COL1A1, COL1A2, PSCA, SCEL, PPL, ACPP, CNFN, and A2ML1) expression trends showed no change. Moreover, higher COL1A1 or COL1A2 expression for ESCC patients showed poor prognosis. Finally, five drugs used for promoting blood coagulation were identified. Probably, these drugs could show anticancer effects by promoting blood coagulation or inhibiting vascular formation in cancers, which offers a novel idea for the treatment of ESCC.


DOCK8 Deficiency Presenting as an IPEX-Like Disorder.
The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (Treg) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing. Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C>T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G→A). Treg cell function was severely compromised by both DOCK8 mutations. DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.


Effects of high-amylose maize starch and butyrylated high-amylose maize starch on azoxymethane-induced intestinal cancer in rats.
Colorectal cancer (CRC) is a major cause of death worldwide. Studies suggest that dietary fibre offers protection perhaps by increasing colonic fermentative production of butyrate. This study examined the importance of butyrate by investigating the effects of resistant starch (RS) and butyrylated-RS on azoxymethane (AOM)-induced CRC in rats. Four groups (n = 30 per group) of Sprague-Dawley rats were fed AIN-93G-based diets containing a standard low-RS maize starch (LAMS), LAMS + 3% tributyrin (LAMST), 10% high-amylose maize starch (HAMS) and 10% butyrylated HAMS (HAMSB) for 4 weeks. Rats were injected once weekly for 2 weeks with 15 mg/kg AOM, maintained on diets for 25 weeks and then killed. Butyrate concentrations in large bowel digesta were higher in rats fed HAMSB than other groups (P < 0.001); levels were similar in HAMS, LAMS and LAMST groups. The proportion of rats developing tumours were lower in HAMS and HAMSB than LAMS (P < 0.05), and the number of tumours per rat were lower in HAMSB than LAMS (P < 0.05). Caecal digesta butyrate pools and concentrations were negatively correlated with tumour size (P < 0.05). Hepatic portal plasma butyrate concentrations were higher (P < 0.001) in the HAMSB compared with other groups and negatively correlated with tumour number per rat (P < 0.009) and total tumour size for each rat (P = 0.05). HAMSB results in higher luminal butyrate than RS alone or tributyrin. This is associated with reduced tumour incidence, number and size in this rat model of CRC supporting the important protective role of butyrate. Interventional strategies designed to maximize luminal butyrate may be of protective benefit in humans.


Rhodium-catalyzed asymmetric addition of arylboronic acids to beta-phthaliminoacrylate esters toward the synthesis of beta-amino acids.
Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to beta-phthaliminoacrylate esters took place efficiently to give high yields of beta-aryl-beta-amino acid esters with 96-99% enantioselectivity, which was realized by use of a hydroxorhodium/chiral diene complex.


[Three cases of adenomatoid tumor of the uterus].
Adenomatoid tumors arising in the uterus are not well-recognized and sometimes mistaken for other benign or malignant neoplasms. This study describes three cases of uterine adenomatoid tumors with clinical, light microscopic, histochemical and electron microscopical studies. Four distinctive histologic patterns (solid, adenoid, angiomatoid, cystic) were identified. Acid mucopolysaccharide was present in three cases and was digested by hyaluronidase. Immunohistochemically, tumor cells were positive for cytokeratin and vimentin. Electron microscopy revealed microvilli, intermediate filaments and dilated intercellular spaces. This gives further support to a mesothelial origin of the adenomatoid tumor. Interestingly, one case showed that the adenomatoid tumor was multiple and one nodule was connected with leiomyomatous nodule. In the other case, the tumor was large 5 x 4 x 4.5 cm). These features were unusual.


Impact of comorbid post traumatic stress disorder on multiple sclerosis in military veterans: A population-based cohort study.
Very little is known regarding the impact of post traumatic stress disorder (PTSD) on the course of multiple sclerosis (MS). To explore the impact of pre-existing PTSD on MS relapses, magnetic resonance imaging (MRI) activity, and disability in a large population-based cohort. Military Veterans with MS and PTSD prior to symptom onset (MSPTSD, n = 96) were identified using the Department of Veterans Affairs MS databases. MSPTSD cases were matched to MS controls without PTSD (n = 95). Number of relapses, number of new T2 lesions and new gadolinium lesions on brain MRI, and neurological disability were abstracted between 2015 and 2019. The mean annualized relapse rate was greater in the MSPTSD group versus controls (0.23 vs 0.06, respectively; p < 0.05), as was the annualized mean number of new T2 and gadolinium-enhancing lesions on brain MRI (0.52 vs 0.16 and 0.29 vs 0.08, respectively; p < 0.05). Disability accrual (time to Disability Status Scale 6.0) was more rapid (23.7 vs 29.5 years, p < 0.05) in relapsing MS patients with PTSD. Patients with MSPTSD have higher disease activity and reach disability endpoints more rapidly than controls. This is the first study to show PTSD as a potentially modifiable risk factor for MS relapses, MRI activity, and disability.


The regulatory switch of F1-ATPase studied by single-molecule FRET in the ABEL Trap.
F1-ATPase is the soluble portion of the membrane-embedded enzyme FoF1-ATP synthase that catalyzes the production of adenosine triphosphate in eukaryotic and eubacterial cells. In reverse, the F1 part can also hydrolyze ATP quickly at three catalytic binding sites. Therefore, catalysis of 'non-productive' ATP hydrolysis by F1 (or FoF1) must be minimized in the cell. In bacteria, the ε subunit is thought to control and block ATP hydrolysis by mechanically inserting its C-terminus into the rotary motor region of F1. We investigate this proposed mechanism by labeling F1 specifically with two fluorophores to monitor the C-terminus of the ε subunit by Förster resonance energy transfer. Single F1 molecules are trapped in solution by an Anti-Brownian electrokinetic trap which keeps the FRET-labeled F1 in place for extended observation times of several hundreds of milliseconds, limited by photobleaching. FRET changes in single F1 and FRET histograms for different biochemical conditions are compared to evaluate the proposed regulatory mechanism.


An Energy-Efficient Strategy and Secure VM Placement Algorithm in Cloud Computing.
One of the important and challenging tasks in cloud computing is to obtain the usefulness of cloud by implementing several specifications for our needs, to meet the present growing demands, and to minimize energy consumption as much as possible and ensure proper utilization of computing resources. An excellent mapping scheme has been derived which maps virtual machines (VMs) to physical machines (PMs), which is also known as virtual machine (VM) placement, and this needs to be implemented. The tremendous diversity of computing resources, tasks, and virtualization processes in the cloud causes the consolidation method to be more complex, tedious, and problematic. An algorithm for reducing energy use and resource allocation is proposed for implementation in this article. This algorithm was developed with the help of a Cloud System Model, which enables mapping between VMs and PMs and among tasks of VMs. The methodology used in this algorithm also supports lowering the number of PMs that are in an active state and optimizes the total time taken to process a set of tasks (also known as makespan time). Using the CloudSim Simulator tool, we evaluated and assessed the energy consumption and makespan time. The results are compiled and then compared graphically with respect to other existing energy-efficient VM placement algorithms.


MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation.
Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and co-morbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis. We performed a global miRNA expression microarray of 723 human and 76 viral mature miRNAs in human adipocytes during differentiation and in subcutaneous fat samples from non-obese (n = 6) and obese with (n = 9) and without (n = 13) Type-2 Diabetes Mellitus (DM-2) women. Changes in adipogenesis-related miRNAs were then validated by RT-PCR. Fifty of 799 miRNAs (6.2%) significantly differed between fat cells from lean and obese subjects. Seventy miRNAs (8.8%) were highly and significantly up or down-regulated in mature adipocytes as compared to pre-adipocytes. Otherwise, 17 of these 799 miRNAs (2.1%) were correlated with anthropometrical (BMI) and/or metabolic (fasting glucose and/or triglycerides) parameters. We identified 11 miRNAs (1.4%) significantly deregulated in subcutaneous fat from obese subjects with and without DM-2. Interestingly, most of these changes were associated with miRNAs also significantly deregulated during adipocyte differentiation. The remarkable inverse miRNA profile revealed for human pre-adipocytes and mature adipocytes hints at a closely crosstalk between miRNAs and adipogenesis. Such candidates may represent biomarkers and therapeutic targets for obesity and obesity-related complications.


Biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy.
Reactive oxygen species (ROS) are usually involved in two opposite procedures related to cancer: initiation, progression and metastasis of cancer, as well as in all non-surgical therapeutic approaches for cancer, including chemotherapy, radiotherapy and photodynamic therapy. This review is concentrated in new therapeutic strategies that take advantage of increased ROS in cancer cells to enhance therapeutic activity and selectivity. Novel biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy are discussed, including optical tweezers and atomic force microscopy. This review highlights how these techniques are playing a critical role in recent and future cancer fighting applications. We can conclude that Biophotonics and nanomedicine are the future for cancer biology and disease management, possessing unique potential for early detection, accurate diagnosis, dosimetry and personalized treatment of biomedical applications targeting cancer.


Advances and Opportunities in Nanoparticle Drug Delivery for Central Nervous System Disorders: A Review of Current Advances.
This narrative review provides an overview of the current advances, challenges, and opportunities in nanoparticle drug delivery for central nervous system (CNS) disorders. The treatment of central nervous system disorders is challenging due to the blood-brain barrier (BBB), which limits the delivery of therapeutic agents to the brain. Promising approaches to address these issues and improve the efficacy of CNS disease therapies are provided by nanoparticle-based drug delivery systems. Nanoparticles, such as liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles, can be modified to enhance targeting, stability, and drug-release patterns. They allow for the encapsulation of a variety of therapeutic compounds and can be functionalized with ligands or antibodies for active targeting, minimizing off-target effects. Additionally, nanoparticles can circumvent drug resistance processes and provide versatile platforms for applications that combine therapeutic and diagnostic functions. Although the delivery of CNS medications using nanoparticles has advanced significantly, there are still challenges to be resolved. These include understanding the BBB interactions, doing long-term safety studies, and scaling up the production. However, improvements in nanotechnology and a deeper comprehension of CNS disorders provide opportunities to enhance treatment results and address unmet medical requirements. Future research and ongoing clinical trials are required to further explore the potential of nanoparticle drug delivery for CNS disorders.


Measurement of the g-tensor of the P700+. signal from deuterated cyanobacterial photosystem I particles.
We report high-field continuous wave EPR spectra of P700+. in preparations obtained from deuterated cyanobacteria (Synechococcus lividus). Measurements were performed with photosystem I (PS-I) preparations, whole cells from cyanobacteria grown in 2H2O, and photosystem II (PS-II) preparations, as well as with protonated PS-I preparations. Because of the significantly improved resolution of our 140-GHz spectrometer (as compared with X- or Q-band EPR) the principal values of the g-tensor of the primary donor P700+. could be resolved and measured with high accuracy as g11 = 2.00304, g22 = 2.00262, and g33 = 2.00232. Other signals arising from Mn2+ and a dark signal from PS-II at g approximately 2.00266 are distinguished from the P700+. g-tensor powder pattern. The measured g values are compared with those of several bacterial reaction center donors.


The Natural History of Radiolucencies Following Uncemented Total Knee Arthroplasty at 9 Years.
Aseptic loosening remains a common cause of failure in total knee arthroplasty (TKA). There is an increased interest in using uncemented TKA to reduce this complication. Radiolucencies (RLs) following uncemented TKA can be concerning. We report on the 9-year history of RLs in patients with uncemented TKA. Twenty-one patients (26 knees) were treated with a cruciate-retaining fully porous coated femur/tibia and cemented patella. At final follow-up, 17 patients (22 knees) were available for review. Average follow-up was 9.6 years, average age was 59.1, and average body mass index was 34.1. X-rays were taken at 6 weeks, 1 year, and at final follow-up. RLs were measured using the Knee Society scoring system and read by two separate surgeons. At 6 weeks, we identified RL in all patients on both the tibia and femur. The majority were beneath the tibial tray and femoral chamfer. At 1 year, 4 femurs and 4 tibias showed new RLs (<2 mm) in similar zones. Eighteen femurs and 18 tibias showed fewer or no change in RLs. At final follow-up, no new tibia or femur developed a new RL. In total, 9 of the 22 tibias and 17 of the 22 femurs had remaining RLs, all less than 2 mm and none were progressive or new. Knee Society Score averaged 92.5 (6 weeks), 95.1 (1 year), and 97.3 (final). RLs are common following uncemented TKA. Many resolve by 1 year. There does not appear to be any association between the presence of RLs and long-term follow-up function in this group of patients.


"Injection first": a unique group of injection drug users in Tijuana, Mexico.
Using baseline data from a study of injection drug users (IDUs) in Tijuana, Mexico (N = 1,052), we identified social and behavioral factors associated with injecting at the same age or earlier than other administration routes of illicit drug use (eg, "injection first") and examined whether this IDU subgroup had riskier drug using and sexual behaviors than other IDUs. Twelve-percent "injected first." Characteristics independently associated with a higher odds of "injection first" included being younger at first injection, injecting heroin as their first drug, being alone at the first injection episode, and having a sexual debut at the same age or earlier as when they initiated drug use; family members' illicit drug use was associated with lower odds of injecting first. When adjusting for age at first injection and number of years injecting, "injection first" IDUs had lower odds of ever overdosing, and ever trading sex. On the other hand, they were less likely to have ever been enrolled in drug treatment, and more commonly obtained their syringes from potentially unsafe sources. In conclusion, a sizable proportion of IDUs in Tijuana injected as their first drug using experience, although evidence that this was a riskier subgroup of IDUs was inconclusive.


CNDP2 Acts as an Activator for Human Ovarian Cancer Growth and Metastasis via the PI3K/AKT Pathway.
The mechanism of tumorigenesis and metastasis of ovarian cancer has not yet been elucidated. This study aimed to investigate the role and molecular mechanism of cytosolic nonspecific dipeptidase 2 in tumorigenesis and metastasis. Cytosolic nonspecific dipeptidase 2 expression in human ovarian cancer tissues and cell lines was assessed with methyl thiazolyl tetrazolium (MTT), clone formation, and transwell assays performed to evaluate the ability of ovarian cancer cells to proliferate and migrate. Nude mice tumor formation experiments were also performed by subcutaneously injecting cells with stable cytosolic nonspecific dipeptidase 2 knockdown and control SKOV3 cells into BALB/c female nude mice to detect changes in PI3K/AKT pathway-related proteins by Western blotting. Cytosolic nonspecific dipeptidase 2 was highly expressed in human ovarian cancer tissues, with its expression associated with pathological data, including ovarian cancer metastasis. A cytosolic nonspecific dipeptidase 2 stable knockdown or ectopic expression ovarian cancer cell model was established and demonstrated that cytosolic nonspecific dipeptidase 2 could promote the proliferation of ovarian cancer cells. Transwell cell migration and invasion assays confirmed that cytosolic nonspecific dipeptidase 2 enhanced cell metastasis in ovarian cancer. Furthermore, in vivo xenograft experiments demonstrated that cytosolic nonspecific dipeptidase 2 can promote the development and progression of ovarian cancer, increasing the expression of phosphorylated PI3K and AKT. Cytosolic nonspecific dipeptidase 2 promotes the occurrence and development of ovarian cancer through the PI3K/AKT signaling pathway.


alpha-Adrenoceptor agonists and the Ca2+-dependence of smooth muscle contraction: evidence for subtypes of receptors or for agonist-dependent differences in the agonist-receptor interaction?
The effects of varying [Ca2+]o on the contraction of smooth muscle by different alpha-adrenoceptor agonists were examined on rat isolated anococcygeus muscle. Agonists were tested in the presence of various [Ca2+]o or 'Ca2+-re-addition curves' were constructed. In some experiments the [Ca2+]free was buffered with EGTA and nitrilotriacetic acid. The components of the response which were revealed were further analysed by using drugs which modify Ca2+ mobilization. Three separate elements in the contractile response were identified: (i) an initial transient contraction, due to intracellular Ca2+ release could be isolated with [Ca2+]o between 1 nmol/l and 3 mumol/l (this could be obtained only with noradrenaline, phenylephrine and amidephrine); (ii) a nifedipine-sensitive response requiring [Ca2+]o of 3 mumol/l or more; (iii) a nifedipine-resistant response requiring [Ca2+]o of 100 mumol/l or more. Presumably (ii) and (iii) involve the entry of Ca2+o: they could be obtained with all agonists tested, including these above, methoxamine, indanidine and xylazine. The results are discussed in relation to the possibility of distinct types of response and their relationship to subgroups of receptors or agonists. It is concluded that there is a continuous spectrum of activity across the agonist range and that this is likely to correlate with 'efficacy' at a single alpha 1 receptor type.


The relation of visfatin with nausea and vomiting in the pregnancy.
The etiology of nausea and vomiting during pregnancy (NVP) is unclear and appears multifactorial. It has been shown that the physiological changes associated with NVP include changes in the levels of adipocytokines. Therefore, we investigated the association of nausea and vomiting during pregnancy with visfatin, β-human chorionic gonadotropin (βHCG), and perceived stress. In this cross-sectional study, 100 nulliparous pregnant women aged 18-45 years were evaluated. Participants completed two questionnaires including the Index of Nausea, Vomiting, and Retching (INVR) and Perceived Stress Scale (PSS) in the three trimesters of pregnancy. They also referred to the laboratory to conduct the biochemical examinations including serum visfatin and βHCG levels in three trimesters. The obtained data were analyzed by SPSS 16 using statistical repeated-measures analysis of variance, Friedman, Bonferroni, and Wilcoxon post hoc tests. Marginal model (method generalized estimating equation [GEE]) was performed to assess the predictors of the INVR in the participants. INVR, PSS, visfatin, and βHCG levels significantly decreased from the first trimester to the third trimester of pregnancy (P ≤ 0.001). As a result of simple marginal model (GEE method), visfatin was predicted log βHCG (P = 0.035). Furthermore, the multiple marginal model revealed that the two predictors of βHCG (P = 0.01) and PSS (P ≤ 0.001) were positively correlated with the INVR. Furthermore, visfatin had an indirect positive effect on INVR. The present study showed that visfatin can be indirectly related with nausea and vomiting throughout pregnancy. Furthermore, it seems that fluctuations in visfatin levels are independent of weight gain during pregnancy.


Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III?
To investigate if frequency of outdoor recreational activity (ORA) predicts cardiovascular disease (CVD) mortality, independent of serum 25(OH)D concentration. Baseline data on ORA and serum 25(OH)D, collected from 11,746 participants aged 30-90 years in the Third National Health and Nutrition Examination Survey during 1988-1994, were linked to the National Death Index for assessment of CVD deaths from baseline through December 2006. CVD mortality as a primary cause of death was assessed during a mean follow up of 12.9 (SD, 4.2) years. There were 1519 CVD deaths during follow up. A strong positive association was observed between frequency of ORA in the last month and serum 25(OH)D (p < 0.001). Compared to participants who did no ORA in the last month, the hazard ratio (HR) of CVD mortality was 0.72 (95% confidence interval 0.58-0.90) for those doing ORA 1-4 times, 0.64 (0.47-0.89) for 5-12 times, 0.70 (0.56-0.89) for 13-30 times and 0.63 (0.47-0.84) for ≥30 times (p-trend < 0.001), in a Cox proportional hazards regression model which included 25(OH)D and CVD risk factors. Serum 25(OH)D was inversely associated with CVD mortality (p-trend, 0.01) in this same model. An inverse association between ORA and CVD mortality was observed independent of 25(OH)D. The underlying mechanism for this association may not involve 25(OH)D hence, further studies are warranted to confirm and investigate the underlying mechanism.


Application potential for some sugar substitutes in some low energy and diabetic foods.
Preparation of acceptable low energy fiber enriched and diabetic jams, cakes and biscuits using different formulas of sucrose substitutes with the partial replacement of wheat flour with bran as a source of dietary fibre, was studied. Special care was paid to evaluate the nutritional plus keeping qualities and the potential effect of the most acceptable formulae from each food stuffs group on the blood glucose level in lean and obese diabetes mellitus patients. It was technologically possible to prepare acceptable, high nutritional diabetic and low energy apricot, guava and strawberry jams and jellies by combinations of sweeteners using xylitol (i.e. xylitol-sorbitol-aspartame and xylitol-fructose). The attainment of a suitable texture may be more difficult in xylitol and sorbitol jams, therefore 0.2 g CaCl2. 2H2O was added. Storage of these jams at 4 degrees C improved their keeping quality significantly (p < 0.05), where the microbial load was less than 20 cells per gram and the products were free from molds and yeasts. Also, high nutritional and acceptable cakes and biscuits for low energy supply and for diabetic subjects can be sweetened with low level of aspartame in combination with fructose, sorbitol and xylitol. Consumption of such low energic and diabetic food items reduces significantly (p < 0.05) the plasma glucose level in lean and obese diabetics. Addition of wheat bran in bakery products not only reduced both energy value of these foods and blood glucose, but it also improved peripheral insulin activity by its system modification.


Erythritol alters microstructure and metabolomic profiles of biofilm composed of Streptococcus gordonii and Porphyromonas gingivalis.
The effects of sugar alcohols such as erythritol, xylitol, and sorbitol on periodontopathic biofilm are poorly understood, though they have often been reported to be non-cariogenic sweeteners. In the present study, we evaluated the efficacy of sugar alcohols for inhibiting periodontopathic biofilm formation using a heterotypic biofilm model composed of an oral inhabitant Streptococcus gordonii and a periodontal pathogen Porphyromonas gingivalis. Confocal microscopic observations showed that the most effective reagent to reduce P. gingivalis accumulation onto an S. gordonii substratum was erythritol, as compared with xylitol and sorbitol. In addition, erythritol moderately suppressed S. gordonii monotypic biofilm formation. To examine the inhibitory effects of erythritol, we analyzed the metabolomic profiles of erythritol-treated P. gingivalis and S. gordonii cells. Metabolome analyses using capillary electrophoresis time-of-flight mass spectrometry revealed that a number of nucleic intermediates and constituents of the extracellular matrix, such as nucleotide sugars, were decreased by erythritol in a dose-dependent manner. Next, comparative analyses of metabolites of erythritol- and sorbitol-treated cells were performed using both organisms to determine the erythritol-specific effects. In P. gingivalis, all detected dipeptides, including Glu-Glu, Ser-Glu, Tyr-Glu, Ala-Ala and Thr-Asp, were significantly decreased by erythritol, whereas they tended to be increased by sorbitol. Meanwhile, sorbitol promoted trehalose 6-phosphate accumulation in S. gordonii cells. These results suggest that erythritol has inhibitory effects on dual species biofilm development via several pathways, including suppression of growth resulting from DNA and RNA depletion, attenuated extracellular matrix production, and alterations of dipeptide acquisition and amino acid metabolism.


Relational aggression in middle childhood predicting adolescent social-psychological adjustment: the role of friendship quality.
The present longitudinal study examined the indirect effect of 6th-grade negative friendship quality on the associations between 5th-grade relational aggression and age 15 social-psychological adjustment (i.e., depressive symptoms and risky behavior). The study consisted of a secondary analysis of the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development using 776 children (M = 10.42 years in 5th grade; 50.4% boys) from the original sample. Using teacher and self-report ratings, relational and physical aggression, friendship quality, depressive symptoms, and risky behavior were measured. Bootstrapping mediation analyses were conducted. Negative friendship quality was found to mediate the association between relational aggression and depressive symptoms as well as between relational aggression and risky behavior, when controlling for physical aggression, gender and age. This longitudinal study identifies possible developmental pathways by which relational aggression and future social psychological adjustment may be linked.


Segregation into layers: a general problem for structural instability under pressure, exemplified by SnH4.
When a molecular compound is thermodynamically unstable (but kinetically persistent) with respect to the elements, structures that contain segregated layers of the elements may be favored at moderate pressures, as a compromise between the potential stability of novel electronic configurations and decomposition into the elements (or other stable compounds). We use stannane, SnH(4), to approach this quite general problem theoretically, since the heat of formation of SnH(4) is so positive. Our ground-state DFT searches for optimal structures begin with slabs formed from 1-4 layers of tin atoms in the β-Sn and bcc configurations, and also slabs of molecular hydrogen or hydrogen atoms, preserving the overall SnH(4) stoichiometry. As argued, segregated layers are an important structural feature in the lower- and moderate-pressure regime (0 and 50 GPa). By 140 GPa (V/V(0)=0.21) the coordination of tin and hydrogen increases and the slabs disappear, as judged from the optimized structures.


Effect of cationic charge and hydrophobic index of cellulose-based polymers on the semipermanent dyestuff process for hair.
In this work, the effects of a new class of polymers generally used in hair and skin cleansing products, the SoftCAT (SofCAT SL and SoftCAT SX), on the dye uptake on the hair fibre and the fading effects has been studied. These polymers, based on quaternary ammonium salts of hydroxyethylcellulose, are cationic products that differ in viscosity, hydrophobic substitution index (HS) and/or cationic substitution (CS, % N). UV-Vis spectroscopy has been used to analyse the extracted dyes from the hair cuticle and the cortex. The results indicate that the presence of polymers in the dye bath improve both the quality of the dyeing process and the anti-fading effect during the washing cycles. This phenomenon is postulated to be attributable to the polymers hydrophobically bonding with the dyes and so facilitating their increased penetration into the hair.


Recent Advances in 19Fluorine Magnetic Resonance Imaging with Perfluorocarbon Emulsions.
The research roots of 19fluorine (19F) magnetic resonance imaging (MRI) date back over 35 years. Over that time span, 1H imaging flourished and was adopted worldwide with an endless array of applications and imaging approaches, making magnetic resonance an indispensable pillar of biomedical diagnostic imaging. For many years during this timeframe, 19F imaging research continued at a slow pace as the various attributes of the technique were explored. However, over the last decade and particularly the last several years, the pace and clinical relevance of 19F imaging has exploded. In part, this is due to advances in MRI instrumentation, 19F/1H coil designs, and ultrafast pulse sequence development for both preclinical and clinical scanners. These achievements, coupled with interest in the molecular imaging of anatomy and physiology, and combined with a cadre of innovative agents, have brought the concept of 19F into early clinical evaluation. In this review, we attempt to provide a slice of this rich history of research and development, with a particular focus on liquid perfluorocarbon compound-based agents.


Proliferative and stimulatory effects of PGA2 on nucleic acids in the adrenal and kidney of squirrel, Funambulus pennanti.
Effects of exogenous prostaglandin A2 (PGA2) on DNA and RNA contents of the adrenal and renal tissues have been examined histochemically. Loss of DNA from the chromatin was observed in both the tissues; however, cells of the capsular regions showed normal cytochemical reactions. Stimulated reactions for RNA in both the tissues but with topographical differences signify the elevated functional capacity. Results further prove the proliferative nature of PGA2. Irregularities in the endogenous secretion of PGA2 and other hormones thus caused, seems to be responsible for these effects.


Addiction Problems, Aggression, and Quality of Life in People with Different Occupations in South Korea.
Addiction is related to aggression and quality of life. This study examined the relationship between these three factors according to occupation group in a mixed urban/rural area to better understand adult addiction problems. This study was a secondary data analysis of cross-sectional data collected by a 2017 regional survey of adults living in Gunsan City, South Korea. The survey included 500 people split into the unemployed (Group1), full-time homemakers (Group2), and primary (Group3), secondary (Group4), and tertiary (Group5) industry workers. Addiction problems and aggression were positively correlated (p < 0.01). Aggression and alcohol use disorder were correlated in Group3 (r = 0.31), Group4 (r = 0.34), and Group5 (r = 0.32), and aggression and smartphone addiction were correlated in Group2 (r = 0.39) and Group4 (r = 0.31). Problem gambling was correlated with aggression in Group5 (r = 0.39). A negative relationship between quality of life and alcohol use disorder occurred in Group1 (r = -0.36). According to the occupation group, the relationships between addiction problems, aggression, and quality of life were different. These findings suggest that addiction management for adults should be implemented in consideration of occupation groups.


Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation.
We compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents. Fasting plasma was analyzed by tandem mass spectrometry, body composition by dual energy X-ray absorptiometry and computed tomography, and total-body lipolysis and substrate oxidation by [(2)H(5)]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp. Long-chain AcylCNs (C18:2-CN to C14:0-CN) were similar among the three groups. Medium- to short-chain AcylCNs (except C8 and C10) were significantly lower in type 2 diabetes compared with NW, and when compared with OB, C2-, C6-, and C10-CN were lower. Amino acid concentrations were lower in type 2 diabetes compared with NW. Fasting lipolysis and FOX were higher in OB and type 2 diabetes compared with NW, and the negative association of FOX to C10:1 disappeared after controlling for adiposity, Tanner stage, and sex. IS was lower in OB and type 2 diabetes with positive associations between IS and arginine, histidine, and serine after adjusting for adiposity, Tanner stage, and sex. These metabolomics results, together with the increased rates of in vivo FOX, are not supportive of defective fatty acid or amino acid metabolism in obesity and type 2 diabetes in youth. Such observations are consistent with early adaptive metabolic plasticity in youth, which over time-with continued obesity and aging-may become dysfunctional, as observed in adults.


High ability of apolipoprotein E4 to stabilize amyloid-β peptide oligomers, the pathological entities responsible for Alzheimer's disease.
Nowadays, the emerging role of amyloid-β peptide (Aβ) oligomers in Alzheimer's disease (AD) is widely accepted, putting aside the old idea that fibrils are the primary entities responsible for the onset of the disease. Besides, carrying the E4 isoform of apolipoprotein E (apoE) represents the highest risk of developing AD. Nevertheless, the involvement of apoE4 in AD remains confusing. The goal of this study was to bring new insights into the role of apoE4 in Aβ aggregation. We used infrared spectroscopy, thioflavin T fluorescence, and Western blots to evaluate the influence of apoE isoforms on Aβ aggregation in vitro. Comparing Aβ controls with Aβ incubated either with the apoE3 or apoE4 isoform, we report a 30% reduction of the Aβ fibrillar content, whereas the oligomeric content is 2 times higher on incubation with the pathological isoform apoE4. ApoE4 would bind and block Aβ in its oligomeric conformation, inhibiting further formation of less toxic fibrillar forms of Aβ. While previous studies mostly correlated E4 with fibrils, our report underlines a link between apoE4 and Aβ oligomers and therefore reconciles apoE4 with the new amyloid cascade hypothesis. Our observations suggest that apoE4 strongly stabilizes Aβ oligomers, the pathological species responsible for Alzheimer's disease.


Energy sources that fuel metabolic processes in protruding finger-like organelles.
Cells possess a variety of organelles with characteristic structure and subcellular localization intimately linked to their specific function. While most are intracellular and found in virtually all eukaryotic cells, there is a small group of organelles of elongated cylindrical shapes in highly specialized cells that protrude into the extracellular space, such as cilia, flagella, and microvilli. The ATP required by intracellular organelles is amply available in the cytosol, largely generated by mitochondria. However, such is not the case for cilia and flagella, whose slender structures cannot accommodate mitochondria. These organelles consume massive amounts of ATP to carry out high energy-demanding functions, such as sensory transduction or motility. ATP from the nearest mitochondria or other reactions within the cell body is severely limited by diffusion and generally insufficient to fuel the entire length of cilia and flagella. These organelles overcome this fuel restriction by local generation of ATP, using mechanisms that vary depending on the nutrients that are available in their particular external environment. Here, we review, with emphasis in mammals, the remarkable adaptations that cilia and flagella use to fuel their metabolic needs. Additionally, we discuss how a decrease in nutrients surrounding olfactory cilia might impair olfaction in COVID-19 patients.


Exosomal arrow (Arr)/lipoprotein receptor protein 6 (LRP6) in Drosophila melanogaster increases the extracellular level of Sol narae (Sona) in a Wnt-independent manner.
Wg/Wnt as a signaling protein binds to Frizzled (Fz) and Arrow (Arr), two Wg co-receptors essential for Wg signaling for cell proliferation, differentiation, and cell survival. Arr has a long extracellular region, a single transmembrane domain and an intracellular region. Here, we report that a new arrm7 mutant is identified in a genetic screen as a suppressor of lethality induced by overexpression of Sol narae (Sona), a secreted metalloprotease in ADAMTS family involved in Wg signaling. arrm7 allele has a premature stop codon, which encodes Arrm7 protein missing the intracellular region. arrm7 clones show cell death phenotype and overexpression of Arrm7 protein also induces cell death. Levels of extracellular Sona were decreased in both arrm7 and arr2 null clones, demonstrating that Arr increases the level of extracellular Sona. Indeed, Arr but not Arrm7, increased levels of Sona in cytoplasm and exosome fraction by inhibiting the lysosomal degradation pathway. Interestingly, Arr itself was identified in the exosome fraction, demonstrating that Arr is secreted to extracellular space. When Sona-expressing S2 cells were treated with exosomal Arr, the extracellular level of active Sona was increased. These results show that exosomal Arr dictates Sona-expressing cells to increase the level of extracellular Sona. This new function of Arr occurred in the absence of Wg because S2 cells do not express Wg. We propose that Arr plays two distinct roles, one as an exosomal protein to increase the level of extracellular Sona in a Wnt-independent manner and the other as a Wg co-receptor in a Wnt-dependent manner.


alphaPS1betaPS integrin receptors regulate the differential distribution of Sog fragments in polarized epithelia.
Bone morphogenetic proteins (BMPs) have important functions during epithelial development. In Drosophila, extracellular Short gastrulation (Sog) limits the action of the BMP family member Decapentaplegic (Dpp). We have shown that Integrin receptors regulate Sog activity and distribution during pupal wing development to direct placement of wing veins. Here, we show that Integrins perform a similar function in the follicular epithelium, impacting Dpp function during oogenesis and embryonic development. As reported for the wing, this effect is specific to mew, which codes for alphaPS1 integrin. Sog is subject to cleavage by metalloproteases, generating fragments with different properties. We also show that Integrins regulate the distribution of C- and N-terminal Sog fragments in both epithelia, suggesting they may regulate the quality of BMP outputs. Our data indicate that alphaPS1betaPS integrin receptors regulate the amount and type of Sog fragments available for diffusion in the extracellular space during oogenesis and pupal wing development.