Polypropylene microtitre plates modified with [Cr(OH)6]3- for enhanced ELISA sensitivity.
Chromium solutions have been used as wet chemical modifiers for polymer microtitre plates used in improving immunoassay performance. However, polypropylene has been excluded from the list of potentially modifiable substrates (AnteoTechnologies, 2015). Here we show that untreated polypropylene microtitre plates can indeed be modified using a [Cr(OH)6]3- complex. Compared to unmodified polypropylene, the chromium modified surfaces demonstrate an up to 4-fold improvement in both assay sensitivity and signal intensity in an antigen capture ELISA. Atomic force microscope (AFM) images indicate that the chromium complex facilitates dispersion of the antibody, reducing aggregation.


Pregnancy, Penile-anal Sex, and Other Sexual Behaviors in the United States, 2011-2015.
We used the US national survey data to examine sexual behavior by pregnancy status and found that, overall, pregnant women did not differ from nonpregnant women in penile-anal sex and associated condom use. Compared with nonpregnant women, pregnant women had lower or similar reports of other sexual behaviors.


[Survey of nurses about compression therapy of acute deep venous thrombosis. Field study in Saxony-Anhalt].
In clinical practice, the compression therapy is an established method for the treatment of acute deep vein thrombosis (DVT). The aim of this study was to clarify the extent to which current guidelines and results of studies done in the field for the treatment of acute DVT--particularly compression therapy--are implemented in clinical practice. All hospitals in Saxony-Anhalt using primary diagnosis and therapy for DVT (n = 34) were informed about a survey in 2007 and the nursing staff of angiology and internistical wards in these hospitals was asked to take part. The collection of data was done with the help of a questionnaire that had been designed and tested for its validity in a specialised hospital. 510 questionnaires were distributed. The response rate of questionnaires was 69 percent. 79 percent of the nursing staff of internistical wards in Saxony-Anhalt and 94 percent of the nursing staff of angiology wards said that patients with acute DVT have initially received a compression bandage. Significant deficits were visible in transferring the knowledge of evidence-based medicine and nursing regarding techniques of compression bandage. The recommended Fischer-Bandage was only put on in exceptional cases in internistical wards (3 percent) and Angiology (2 percent). Compression stockings were not a suitable method into the treatment of acute deep vein thrombosis of Angiology. 21 percent of the nursing staff of internistical wards said that they have initially applied compression stockings. The treatment of acute DVT is important in clinical practice. The compression bandage should be effectively put on the leg. The quality of care and long-term compliance of the patients could be increased this way, leading to prevention of post thrombotic syndrome (PTS) and reduction the duration of patients stay in the clinics.


Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling.
The bone is the most common metastatic site of breast cancer. Bone metastasis causes pain, pathologic fractures, and severely reduces the quality of life. Breast cancer causes osteolytic bone metastasis, which is dependent on osteoclast-mediated bone resorption. While current treatments rely on palliative anti-resorptive agents, there is a need to develop a drug based on potential alternative therapies. This study is the first to determine that wedelolactone (WDL), a natural coumarin isolated from plants, can inhibit breast cancer-mediated osteoclastogenesis. Osteoclasts were generated from human CD14(+) monocytes cultured with M-CSF/RANKL and WDL suppressed human osteoclast differentiation and activity in vitro in a dose-dependent manner. Moreover, WDL inhibited the upregulation of osteoclasts stimulated by MDA‑MB‑231 breast cancer cells. The activity of WDL on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of Akt/mammalian target of the rapamycin signaling pathway (mTOR). Blocking Akt and mTOR by specific inhibitors significantly decreased osteoclast differentiation and bone resorption. Furthermore, WDL regulated breast cancer-enhanced interaction of osteoblasts and osteoclasts by decreasing M-CSF expression in MDA‑MB‑231-stimulated osteoblasts. Thus, this study suggests that WDL may be a potential natural agent for preventing and treating bone destruction in patients with bone metastasis due to breast cancer.


Emerging drugs for asthma.
Current therapies for asthma are aimed at controlling disease symptoms and for the majority of asthmatics inhaled corticosteroid anti-inflammatory therapy is effective. However, this approach requires life-time therapy while a subset of patients remains symptomatic despite optimal treatment creating a clear unmet medical need. It is recognised that airway inflammation is key to asthma pathogenesis. Biopharmaceutical approaches may identify new therapies that target key cells and mediators that drive the inflammatory responses in the asthmatic lung. Such an approach may provide disease-modifying treatments. Significant areas of drug development include humanised monoclonal antibodies (mAb) for asthma therapy including those against IgE, IL-4 and IL-5. Asthma-relevant cytokines or chemokines have been targeted in a number of other ways. These include the use of humanised receptor blocking mAb or the removal of cytokines or chemokines via their binding to soluble receptor constructs. Small-molecule receptor antagonists also target receptors or the cellular signal transduction pathways that are activated following cytokine or chemokine receptor ligation. Another approach is to target asthma relevant mediators or the pathways controlling pro-inflammatory leukocyte accumulation within the asthmatic lung. This review will discuss the current status, therapeutic potential and potential problems of these novel drug developments in asthma therapy. Current therapies for asthma are aimed at controlling disease symptoms, and for the majority of asthmatics inhaled corticosteroid anti-inflammatory therapy is effective. However, this approach requires lifetime therapy; and a subset of patients remains symptomatic despite optimal treatment, creating a clear unmet medical need. It is recognised that airway inflammation is key to asthma pathogenesis. Biopharmaceutical approaches may identify new therapies that target key cells and mediators that drive the inflammatory responses in the asthmatic lung. Such an approach may provide disease-modifying treatments. Significant areas of drug development include humanised mAb for asthma therapy, including those against IgE, IL-4 and IL-5. Asthma-relevant cytokines or chemokines have been targeted in a number of other ways. These include the use of humanised receptor blocking mAb or the removal of cytokines or chemokines via their binding to soluble receptor constructs. Small-molecule receptor antagonists also target receptors or the cellular signal transduction pathways that are activated following cytokine or chemokine receptor ligation. Another approach is to target asthma-relevant mediators, or the pathways controlling pro-inflammatory leukocyte accumulation within the asthmatic lung. This review will discuss the current status, therapeutic potential and potential problems of these novel drug developments in asthma therapy.


Careful neuropsychological testing reveals a novel genetic marker, GSTO1*C, linked to the pre-stage of Alzheimer's disease.
Approximately 30 million people currently suffer from late-onset Alzheimer's disease (LOAD) worldwide. Twin studies demonstrated that 60 to 80% of LOAD is genetically determined, 20% of which remaining unassigned. This case-control study included 118 cognitively healthy controls, 52 patients with mild cognitive impairment (MCI; the pre-stage of LOAD) and 71 LOAD patients. The participants were genotyped for the genetic LOAD marker apolipoprotein E4 (APOE4) and the single-nucleotide polymorphism rs4925 in glutathione S-transferase omega-1 (GSTO1). Additive logistic regression showed a novel, statistically significant association of the major allele GSTO1*C with MCI (OR1.9; p = 0.032). However, identification of significant SNP-disease relations required well-defined study groups. When classifying participants solely by the short Mini Mental State examination (MMSE), the associations of GSTO1*C and the reference marker APOE4 with MCI were cancelled. Moreover, even identifying only the control group by MMSE nullified a statistically significant association (OR1.8; p = 0.045) between GSTO1*C and LOAD. In contrast, these statistical relations were retained when the detailed Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) test battery was used. Hence, besides proposing rs4925 as a genetic marker for cognitive impairment, this work also emphasized the importance of carefully characterized controls in addition to well-diagnosed patients in case-control studies.


COVID-19 in Saudi Patients With Sickle Cell Disease: A Retrospective Multi-Center Study.
Background The prevalence of sickle cell disease (SCD) within Saudi Arabia is relatively high, with an estimated 145/10,000 cases. There is an urgent need for researching many aspects of the Coronavirus disease of 2019 (COVID-19) due to the widespread of the virus among SCD patients in Saudi Arabia. The aim of this study is to determine how COVID-19 affects SCD patients in order to reach the best strategy for their management protocols. Methods This is a retrospective chart review study from a multi-center in Saudi Arabia that evaluated a total of 33 patients with sickle cell anemia/disease who were confirmed to have COVID-19. The diagnosis of COVID-19 was confirmed by using the reverse transcription-polymerase chain reaction (RT-PCR) tests based on the nasopharyngeal swabs of the included patients. Results The mean age of patients was 10.75+9.11 years, and nearly all patients (n= 32; 96.9%) were Saudi, and 48.4% of them were females. Twenty-two patients were admitted (59.5%); the main reasons for admission included vaso-occlusive crisis (VOC) only (n= 6; 27.3%), fever (n= 6; 27.3%), acute chest syndrome (n= 5; 22.7%), and VOC combined with other conditions (n= 4; 18.2%). During hospitalization, 54.1% of the patients received at least one medication, while antibiotics (54.1%), analgesia (32.4%), anticoagulants (16.2%), and steroids (16.2%) were the most commonly administered drugs. The mean length of hospitalization was 7.6±4.5 days, with only one patient (2.7%) requiring intensive care unit admission and assisted ventilation. Conclusion The overall prognosis was good since only one patient has passed away, while all others recovered and, subsequently, were discharged. Manifestations, laboratory investigations, and management modalities should be utilized promptly to enhance the prognosis and obtain better outcomes.


Preoperative Smoking Cessation as a Durable Form of Long-Term Smoking Cessation.
Smokers who undergo total joint arthroplasty (TJA) face increased rates of medical and surgical complications that can be reduced by preoperative smoking cessation. We investigated the long-term durability of preoperative smoking cessation among TJA patients. Twenty-seven TJA patients who were identified as having an active history of smoking at the preoperative appointment before TJA consented to telephone survey about their perioperative and current smoking status. Average time from operation to survey was 3.7 years. Of the 27 patients, 21 (77.8%) were identified as having quit smoking prior to surgery. Of these 21 patients, 10 (47.6%) self-reported continued abstinence from smoking at the time of survey. Our cessation rate was significantly lower than reported long-term smoking cessation rates with standard therapies (p < 0.001). Our results suggest that preoperative counseling and a requirement for smoking-cessation prior to elective TJA may have long-term durability that exceeds that of popular reported methods. (Journal of Surgical Orthopaedic Advances 29(2):103-105, 2020).


The influence of genetic explanations of type 2 diabetes on patients' attitudes to prevention, treatment and personal responsibility for health.
It is widely accepted that type 2 diabetes is caused by an interaction of both lifestyle and genetic factors. However, the impact of explaining disease aetiology as primarily genetic or environmental is relatively unexplored for common chronic multi-factorial conditions. This study investigates whether perceiving the cause of type 2 diabetes as primarily genetic or environmental influences attitudes towards the controllability of the condition. Using a between-participants vignette-based experimental survey design, 200 participants aged 40 years and above from a primary care setting responded to a vignette which implied the cause of diabetes as being predominantly genetic or environmental. Attitudes towards personal responsibility, prevention and treatment were measured using an attitude questionnaire. There was a significant interaction effect between perceived aetiology and family history on attitude to treatment; participants with a family history of type 2 diabetes perceived treatment as less effective if they read the genetic vignette, but those without a family history did not (p < 0.05). The findings also indicated that an individual was perceived as less responsible for the development of type 2 diabetes (p < 0.05) when participants (regardless of family history) read a vignette with an implied genetic causation. Awareness by health professionals of the impact of genetic attributions in disease aetiology is fundamental when encouraging positive attitudes to personal responsibility for lifestyle change and treatment for the condition. These findings may impact the way preventative health messages are tailored to people depending on their family history of diabetes.


Preliminary toxicity studies on bis-[beta-(N,N-dimorpholino) ethyl] selenide (MOSE). A new radioimaging agent.
The present study describes the acute toxicity of MOSE, a proposed radioimaging agent for brain scintigraphy . Acute intraperitoneal administration of MOSE in mice revealed an LD50 between 1.35 and 6.25 g/kg, with convulsions preceding death. Intravenous administration of MOSE in rats resulted in an LD50 between 400 and 800 mg/kg, with death also preceded by convulsions. The rabbit was more sensitive to the acute effects of MOSE than the rat. The LD50 for MOSE given i.v. in the rabbit was 80 mg/kg. The predominant toxic sign was convulsions, which immediately preceded death at high doses. At intermediate doses convulsions were elicited, followed by a period of lethargy which gave way to hyperactivity on the following day. Normal appearances were restored within a week. Hematology and blood chemistries were similar to controls, except for increased serum LDH in animals receiving MOSE when sampled two weeks after dosing. Repeated administration of MOSE by the intravenous route in rabbits at a dose rate of 1 mg/kg/da, five days per week for two weeks, resulted in no signs of toxicity. Hematology, clinical chemistry, and histology revealed no changes in animals receiving MOSE when compared to control. It was concluded that barring any unusual susceptibility in man, the proposed diagnostic dose to man is unlikely to precipitate any acute toxic effects.


Treatment of panic disorder with imipramine alone.
Ten patients with panic disorder were treated solely with imipramine in an open pilot trial. All patients reported cessation of panic attacks and considerable overall improvement. Four patients who took medication 5 months or longer reported marked overall improvement.


Services provided for preschool-aged children with suspected amblyopia.
Little is known about the pattern and variation of care offered to preschool-aged children who have had an abnormal vision screening test. To evaluate the variations in pediatric eye care services and availability of optometrists and ophthalmologists for preschool-aged patients, referral patterns, and barriers to providing care as perceived by eye care specialists. A survey was mailed to 542 ophthalmologists and a random sample of 501 optometrists actively practicing in Michigan. The response rate was 65% (optometrists, 75%; ophthalmologists, 57%). More optometrists than ophthalmologists evaluated preschool-aged children (97% vs 79%; P < .001). Of these, most managed amblyopia (80% vs 77%; P = .372) and strabismus (89% vs 80%; P = .002) themselves. Fewer optometrists than ophthalmologists dilated eyes routinely during the first evaluation of a preschool-aged child (39% vs 93%; P < .001). The leading barrier to care for preschool-aged children reported by both optometrists and ophthalmologists was difficulty of the examination (25% vs 23%; P = .501). Optometrists reported that most of their patients were referred from community-based screening programs or by parent self-referral. Ophthalmologists reported that most of their preschool-aged patients were referred from primary care providers. There are different sources of referrals for optometrists and ophthalmologists. Although most eye care specialists treat amblyopia, the types of care offered by optometrists and ophthalmologists differ. Future studies should address the impact that these patterns have on outcomes and cost. The results of these studies should be shared with those responsible for screening.


Role of Graphene in Reducing Fatigue Damage in Cu/Gr Nanolayered Composite.
Nanoscale metal/graphene nanolayered composite is known to have ultrahigh strength as the graphene effectively blocks dislocations from penetrating through the metal/graphene interface. The same graphene interface, which has a strong sp2 bonding, can simultaneously serve as an effective interface for deflecting the fatigue cracks that are generated under cyclic bendings. In this study, Cu/Gr composite with repeat layer spacing of 100 nm was tested for bending fatigue at 1.6% and 3.1% strain up to 1,000,000 cycles that showed for the first time a 5-6 times enhancement in fatigue resistance compared to the conventional Cu thin film. Fatigue cracks that are generated within the Cu layer were stopped by the graphene interface, which are evidenced by cross-sectional scanning electron microscopy and transmission electron microscopy images. Molecular dynamics simulations for uniaxial tension of Cu/Gr showed limited accumulation of dislocations at the film/substrate interface, which makes the fatigue crack formation and propagation through thickness of the film difficult in this materials system.


Fatal bupropion overdose.
Bupropion is a unique monocyclic antidepressant that has been known to cause seizures in high therapeutic doses and in acute overdoses. Death due to ingestion, however, is a rare occurrence. We report a case of a 26-year-old man who ingested 23 g bupropion, developed seizures and hypoxia, and presented in cardiac arrest. The patient was resuscitated in the emergency department, but died 4 d after supportive intensive care. Bupropion overdose may lead to recurrent seizures, hypoxia and death. Aggressive management of severe bupropion overdose is recommended.


Spectral density of fluctuations in fractional bistable Klein-Kramers systems.
We investigate the stationary spectral density of fractional bistable Klein-Kramers systems. First, we deduce a dissipation-fluctuation relation between the stationary spectral density at thermal equilibrium and the linear response of the system to an applied perturbation. Second, we describe how to obtain the linear dynamic susceptibility from the method of moments, and thus we derive the fluctuating spectral density from the dissipation-fluctuation relation. Finally, we exhibit the structure of this fluctuating spectral distribution and explore the effect of the subdiffusion on it. Compared with the standard bistable Klein-Kramers systems, our observation on the spectral distribution in fractional systems reveals that the subdiffusion weakens the oscillatory components of the intrawell oscillation and the above-barrier motion. This phenomenon should reflect a fact that the particles tend to stand still in separate wells in subdiffusive processes.


Wound Infection with Multi-Drug Resistant Clostridium Perfringens: A Case Study.
Wound infections are among public health problems worldwide. However, progress has been made in improving surgical techniques and antibiotic treatments. Misuse/overuse of antibiotics to prevent and treat bacterial infections eventually leads to increased bacterial resistance with rising incidences of multi-drug resistant (MDR) bacterial strains. The wider dissemination of antibiotics may ultimately result in ineffectiveness to antibiotic therapy, thereby complicating/graving the outcome of a patient. In the present study, a 60-year-old male patient having wound infection with MDR bacterium that ultimately required surgical amputation of the toe was investigated. For the confirmation of MDR bacterium, two culture media viz., MacConkeyAgar and Mueller Hinton Agar media were used. The sensitivity of the isolated strain for various antibiotics was tested using the disc diffusion method. The wound sample was found positive for Gram-positive bacterium that was identified as Clostridium Perfringens. The bacterium was screened for 40 antibiotics, and among all the antibiotics, it was found sensitive for only Piperacillin/Tazobactam antibiotic combination. C. perfringens bacterium caused the gas gangrene in the infected wound part of the patient. Amputation of the gangrene -affected foot part was performed by surgery, and with good medical care, the person recovered fast. To the best of our knowledge, this is the first-ever report of MDR C. perfringens single isolate harboring resistance against at least 40 antibiotics tested. More research is needed to develop really new and effective medicines that do not cross-react with antibiotics now in use and have robust activity against MDR organisms.


Cathepsin L function in insect moulting: molecular cloning and functional analysis in cotton bollworm, Helicoverpa armigera.
Moulting is an essential process of insect development but little is known about cysteine proteases in the process. Here, we detail a proteolytic activity profile from fifth larval instar to new pupae of the lepidopteran Helicoverpa armigera. At fifth to sixth instar moulting, the activities were significantly higher than those in non-moulting stages, and were inhibited by the cysteine protease inhibitor, 2S, 3S-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester (E-64), or by the cathepsin L-selective inhibitor CLIK148. Further, a 1513 bp cathepsin L cDNA (Har-CL) was isolated from the H. armigera larval cuticle and epidermis layer. Har-CL gene expression, which is correlated closely with ecdysone, was higher during larval moulting. Injection of E-64 or CLIK148 resulted in delayed fifth to sixth instar moulting, suggesting an essential role for cathepsin L in larval moulting.


Hepatoprotective and nephroprotective effects of Tessaria integrifolia Ruiz and Pav. on diclofenac-induced toxicity in rats.
Tessaria integrifolia Ruiz and Pav. (also known as "Pájaro bobo") is known for its medicinal properties, including antiulcer, antiasthmatic, leishmanicidal, antipyretic, antispasmodic, diuretic, anti-inflammatory, analgesic, and hepatoprotective effects. Therefore, we aimed to evaluate its hepatoprotective and nephroprotective effects using a rat model of diclofenac-induced toxicity. We administered three different doses of the methanolic extract of T. integrifolia (100, 200, and 400 mg/kg/day orally) and compared them with the commercial medicine silymarin (100 mg/kg orally). The rats received the T. integrifolia extracts for 5 days, and on days 3 and 4, 1 h after receiving the extracts, diclofenac was administered intraperitoneally at a dose of 50 mg/kg. The animals were euthanized 48 h after the last diclofenac injection, and blood samples were obtained to measure biochemical parameters related to liver and kidney function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, cholesterol, triglycerides, creatinine, and urea. Kidney and liver tissues were preserved in 10% formaldehyde and sent for histopathological analysis. The results show that T. integrifolia has hepatoprotective and nephroprotective effects. These effects are verified by the lower blood levels of ALT, AST, urea, and creatinine compared to the diclofenac group, which exhibited elevated biochemical parameters. In addition, histopathological analysis showed that the groups that received T. integrifolia did not display necrosis or infiltration, which were observed in the diclofenac group. The methanolic extract of T. integrifolia has hepatoprotective and nephroprotective effects, with the highest protective activity observed at a dose of 400 mg/kg/day.


[Pathological and molecular analyses of mammary tumors induced in HTLV-I pX transgenic rats].
The pX gene of human T-cell leukemia virus type I (HTLV-I) is known to be a potent transactivator of the viral gene and the host genes which are important for cell proliferation in vitro. It has been reported that various diseases occur in transgenic mice harboring either tax, pX, or env-pX gene, such as mesenchymal tumor, neurofibroma, thymic atrophy, muscle degeneration, exocrinopathy and arthropathy. We previously demonstrated that rat but not mouse CD4 positive T cells could be easily infected and immortalized by HTLV-I and infectious transmission of HTLV-I induced HAM/TSP-like myelopathy in WKAH rats after long incubation periods of 16 months. These observations prompted us to produce a series of transgenic rats that expressed the pX gene products under the control of mouse H-2Kd promotor in order to evaluate further the biological and pathological function of the pX gene in vivo. In various tissues of pX transgenic rats (pX rats), pX mRNA was constitutively expressed irrespective of age. PX rats developed mammary tumors with massive infiltration by neutrophils as early as 9 months of age. Pathological and immunohistochemical examination revealed that the tumors were undifferentiated carcinomas of the mammary gland origin. They were transplantable into pX rats, but not into normal syngenic rats. High levels of mRNA expression of not only the pX transgene but also the host genes such as Gro (melanoma growth-stimulatory activity/KC), MIP-2 (macrophage inflammatory protein-2) and IL-1 alpha were demonstrated in the tumor tissues. Gro and MIP-2 which were known as IL-8 families were likely to be produced by tumor cells and appeared to be responsible for neutrophil infiltration in the tumor tissues. Lastly, pX rats described here appear to be suitable animal models for elucidating mechanisms involved in the tumorigenesis and the transactivation of the cellular genes by HTLV-I, especially by the pX gene products in vivo.


[Pain in children: specific aspects].
Childhood pain is still poorly understood, neglected and undertreated. The neurophysiological mechanisms of nociception exist before birth. The experience of pain develops during childhood. Its symptomatology has been detailed: sharp emotional reactions and signs of stress during acute pain, antalgic posture, psychomotor atony and denial when pain is prolonged. Specific tools for evaluation are available. Treatment generally calls for the use of peripheral analgesics, and increased intensity of pain can require administration of morphine.


Dental diseases and gastroenterology.
Recently, the relationship between digestive diseases and oral diseases has been a focus of interest. Physicians and dentists should not simply diagnose diseases without understanding the possible relationships between the mouth and digestive system, such as double cancers in oral cavity and esophagus or stomach. Physicians should learn to examine the mouth systematically. On the other hand, dentists should not only treat dental caries, periodontitis, and denture problems, but should also study medical knowledge in order to develop dental treatment for total oral health care. In other words, dentists should become oral physicians or stomatologists. In this paper, we describe how digestive diseases relate to oral diseases and the important systemic findings you can deduce from oral findings. We hope that the knowledge presented here will be helpful for dentists and physicians in their daily practice.


Cooling-evoked hemodynamic perturbations facilitate sympathetic activity with subsequent myogenic vascular oscillations via alpha2-adrenergic receptors.
This study extends our previous work by examining the effects of alpha2-adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variability. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and heart rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of power spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethidine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge.


Prednisolone Delivery Platforms: Capsules and Beads Combination for a Right Timing Therapy.
In this work, a platform of alginate beads loaded with Prednisolone in hypromellose/gellan gum capsules (F6/Cps) able to delay steroidal anti-inflammatory drug (SAID) release as needed for chronotherapy of rheumatoid arthritis is proposed. Rheumatoid arthritis, showing a worsening in symptoms in the morning upon waking, is a pathology that can benefit from chronotherapy. With the aim to maximize prednisolone therapeutic action allowing the right timing of glucocorticoid therapy, different engineered microparticles (gel-beads) were manufactured using prilling (laminar jet break-up) as micro-encapsulation technique and Zn-alginate as gastroresistant carrier. Starting from various feed solutions and process parameters, the effect of the variables on particles size, morphology, solid state properties and drug release was studied. The optimization of operative and prilling/ionotropic gelation variables led to microspheres with almost spherical shape and a narrow dimensional range. The feed solution with the highest alginate (2.5% w/v) amount and drug/polymer ratio (1:5 w/w) gave rise to the highest encapsulation efficiency (78.5%) as in F6 formulation. As to drug release, F6 exhibited an interesting dissolution profile, releasing about 24% of the drug in simulated gastric fluid followed by a more sustained profile in simulated intestinal fluid. #F6, acting as a gastro-resistant and delayed release formulation, was selected for in vivo studies on male Wistar rats by means of a carrageenan-induced oedema model. Finally, this efficacious formulation was used as core material for the development of a final dosage form: F6/Cps allowed to significantly reduce prednisolone release in simulated gastric fluid (12.6%) and delayed drug release up to about 390 minutes.


Molecular cloning and tissue distribution of Crh and Pomc mRNA in the fat-tailed dunnart (Sminthopsis crassicaudata), an Australian marsupial.
Like all vertebrates, marsupials respond to stressors with the activation of the hypothalamo-pituitary-adrenal axis. However, peptides operating at the higher regulatory levels of this hormonal system, i.e. corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), have not been investigated in marsupials. Here we report the molecular cloning of the precursor cDNAs of CRH (prepro-CRH) and of ACTH (proopiomelanocortin; POMC) in an Australian marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata). Dunnart POMC and prepro-CRH are predicted to be peptides of 399 and 200 amino acids, respectively. While the ACTH and β-endorphin sequences within the POMC sequence are highly conserved, the POMC sequence shows some unique features in this species, and perhaps all Australian marsupials, including the loss of a γ-melanotropin sequence and duplications of the ACTH sequence. Mature dunnart CRH is identical to CRH in human, mouse, rat and chicken. Pomc and Crh mRNA is mainly expressed in dunnart pituitary gland and brain, respectively, but both are also present in a range of peripheral tissues.


Suppression of normal hematopoiesis in acute leukemia: effect of leukemic cells on bone marrow stromal cells and hematopoietic progenitor cells.
Effects of leukemic cells (LC) on bone marrow stromal cells and myeloid progenitor cells (CFU-C) were studied in vitro, using LC lines with different lineage characteristics. LC and/or LC-conditioned medium (LC-CM) inhibited the growth of a stromal cell line, KM-101, and adherent cells of a long-term bone marrow culture (LTBMC) established from normal bone marrow. The inhibition was more prominent when LC were cocultured directly with KM-101 cells than when LC were cultured separate from the KM-101 cell layer via membrane filtration, or when LC-CM was added to KM-101 cells or LTBMC. LC-CM also exerted an inhibitory effect on the ability of LTBMC adherent cells to bind CFU-C. Furthermore, LC-CM inhibited the growth and survival of early and late CFU-C, but not the growth of LC. All these inhibitory effects were seen irrespective of the lineage characteristics of LC, but not seen with CM prepared from normal bone marrow immature granulocytes or peripheral blood lymphocytes. Neither tumor necrosis factor-alpha nor interferon-alpha was detected in these LC-CM. These findings suggest that LC suppress normal hematopoiesis through the release of undefined substance(s) inhibiting the growth and/or survival of stromal cells and hemopoietic progenitor cells as well as the function of stromal cells.


Women's reactions to HPV diagnosis: insights from in-depth interviews.
Research links certain types of the human papillomavirus (HPV) to subsequent development of cervical cancer. Women (n=52) recently diagnosed with HPV following an abnormal Pap smear participated in in-depth interviews to explore their knowledge of HPV, their emotional responses to diagnosis, and the extent of their disclosure of their HPV diagnosis to others. Women had many knowledge deficits about HPV. Emotions related primarily to stigma, fear, self-blame, powerlessness, and anger. Most women disclosed their disease to significant others, usually to a sexual partner. Women's lack of accurate knowledge may contribute to the array of emotions they experience. Whereas education about HPV may reduce the potency of these emotions, information alone may be inadequate for achieving optimal patient care. Health care providers can be important in treating the emotional elements associated with diagnosis as well as the condition itself.


Introduction to Fillers.
Over the last few years, injectable soft-tissue fillers have become an integral part of cosmetic therapy, with a wide array of products designed to fill lines and folds and revolumize the face. This review describes cosmetic fillers currently approved by the Food and Drug Administration and discusses new agents under investigation for use in the United States. Because of product refinements over the last few years-greater ease of use and longevity, the flexibility of multiple formulations within one line of products, and the ability to reverse poor clinical outcomes-practitioners have gravitated toward the use of biodegradable agents that stimulate neocollagenesis for sustained aesthetic improvements lasting up to a year or more with minimal side effects. Permanent implants provide long-lasting results but are associated with greater potential risk of complications and require the skilled hand of the experienced injector. A variety of biodegradable and nonbiodegradable filling agents are available or under investigation in the United States. Choice of product depends on injector preference and the area to be filled. Although permanent agents offer significant clinical benefits, modern biodegradable fillers are durable and often reversible in the event of adverse effects.


Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling.
The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell migration. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo. Overexpression of the PRIP pleckstrin homology domain, a PI(4,5)P2 binding motif, in MCF-7 cells caused significant suppression of cell migration. Consistent with these results, in comparison with wild-type cells, Prip-deficient mouse embryonic fibroblasts exhibited increased cell migration, and this was significantly attenuated upon transfection with a siRNA targeting p110α, a catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI(3,4,5)P3 production was decreased in Prip-overexpressing MCF-7 and BT-549 cells. PI3K binding to PI(4,5)P2 was significantly inhibited by recombinant PRIP in vitro, and thus the activity of PI3K was downregulated. Collectively, PRIP regulates the production of PI(3,4,5)P3 from PI(4,5)P2 by PI3K, and the suppressor activity of PRIP in PI(4,5)P2 metabolism regulates the tumour migration, suggesting PRIP as a promising target for protection against metastatic progression.


Geriatric referral patterns for physical therapy: a descriptive analysis.
The purposes of this study were to: (1) describe older adults being seen for physical therapy, (2) identify the most prevalent physician orders and physical therapy interventions, and (3) compare these results across US regions. A written questionnaire was mailed to a random sample of 1600 therapists. Therapists completed information for up to 10 patients including classification of diagnosis according to the Guide to Physical Therapist Practice. Descriptive analyses were performed. 118 therapists provided information on 839 patients. More of the patients were women (65%) than men (35%); their average age was 76.4 years. Most patients were seen in the outpatient setting (56%) and over 70% were classified into one of the musculoskeletal diagnostic categories. "Evaluate and treat" was present in 66.2% of the physician orders. The 6 most frequently performed interventions were in the therapeutic exercise category. Many physical therapists, even those who may not consider themselves geriatric physical therapists, are seeing older adults in a variety of settings. Knowledge about the diverse needs of older adults, therefore, is important for clinicians and students to meet the rising demand for quality physical therapy for this population.


Pathology as it relates to ear surgery. V. Ossiculoplasty.
In the present state of the art, autografts and homografts behave equally well in ossiculoplasty. Allografts are to be reserved for cases in which these two are in short supply. Bone grafts, autogenous and homologous, did not show gross changes in physical characters or surface structure. No obvious remodelling occurred in the grafts eight years after their insertion in the middle-ear. Microscopically, progressive deposition of new bone occurred, resulting in narrowing of the bone lacunae and bone marrow spaces. Cartilage autografts underwent progressive ischemic calcification in the middle-ear. No evidence of erosion, dissolution or remodelling was apparent eight years after their insertion in the middle-ear. Plastipore prostheses resulted in a consistent local fibrous tissue and foreign body reaction. Micro-disintegration of the prostheses is questionable. No gross changes in the physical characters or surface structure of these prostheses was evident 34 months after their insertion in the middle-ear. Inadequate hearing results following ossiculoplasty in this series were most commonly due to loss of contact between the graft and the remaining ossicles. Eustachian tube dysfunction was another possibility. Dissolution of the grafts was not the cause in any of our cases.


CORP (COlchicine for Recurrent Pericarditis) and CORP-2 trials--two randomized placebo-controlled trials evaluating the clinical benefits of colchicine as adjunct to conventional therapy in the treatment and prevention of recurrent pericarditis: study design and rationale.
Colchicine appears to be safe and effective in the treatment and prevention of recurrent pericarditis after failure of conventional therapies in case reports and non-randomized observational studies without control groups. On this basis, colchicine has been proposed as a therapeutic choice in the 2004 guidelines of the European Society of Cardiology. However, the exact number of responders is unknown, and no randomized placebo-controlled trial is available to guide the management of recurrent pericarditis. Moreover, some authors recommend the use of the drug at the first recurrence, whereas others propose to consider the drug only after failure of conventional therapies for the second or subsequent recurrence. The CORP trial will enroll 120 patients in a prospective, randomized, double-blind, multicentre investigation of colchicine compared with placebo in patients with a first episode of recurrent pericarditis. In the CORP-2 trial, 240 patients will be enrolled in a prospective, randomized, double-blind, multicentre investigation of colchicine compared with placebo in patients with two or more recurrences. In both trials, the primary efficacy end-point is the recurrence rate at 18 months, the secondary end-points are symptom persistence at 72 h, remission rate at 1 week, number of recurrences, time to recurrence, disease-related hospitalization, cardiac tamponade and constrictive pericarditis. The CORP and CORP-2 trials will be the first randomized placebo-controlled trials in this area. These trials will provide important evidence regarding the possible benefit of the early use of colchicine for the treatment and prevention of recurrent pericarditis.


Sequential muscle activity and its functional role in the upper extremity and trunk during overarm throwing.
The proximal-to-distal segmental sequence has been identified in many sports activities, including baseball pitching and ball kicking. However, proximal-to-distal sequential muscle activity has not been identified. The aims of this study were to establish whether sequential muscle activity does occur and, if it does, to determine its functional role. We recorded surface electromyograms (EMGs) for 17 muscles from the upper extremity and abdomen during overarm throwing and detected the onset and peak times as indices of muscle activity. The following electromyographic properties were commonly identified in the participants. First, sequential muscle activity was observed from the scapular protractors to the shoulder horizontal flexors and from the shoulder horizontal flexors to the elbow extensor, but not from the elbow extensor to the wrist flexor or forearm pronator. Secondly, the external oblique contralateral to the throwing arm became activated before the ipsilateral external oblique. This sequence is considered to be very effective for the generation of high force and energy in the trunk. Thirdly, the ipsilateral external oblique began its activity almost at foot strike. Finally, the main activity of the rectus abdominis appeared just before the point of release.


Selenium is inversely associated with bladder cancer risk: a report from the Belgian case-control study on bladder cancer.
Selenium is an essential trace element with suspected anticarcinogenic properties in humans. To date, eight epidemiological studies have examined the association between serum selenium concentration and bladder cancer risk. The authors carried out a population case-control study in 178 cases and 362 controls to assess the relationship between bladder cancer risk and selenium serum concentrations. Unconditional logistic regression was calculated to determine odds ratios (OR) for bladder cancer occurrence with corresponding 95% confidence intervals (95% CI). Effect modification by smoking status, low fruit and vegetable intake, retinol equivalent, vitamin C, vitamin E and total antioxidant status were also assessed. Serum selenium level was negatively associated with bladder cancer risk. After adjustment for sex, age, smoking and occupational exposure, the OR was 0.48 (95% CI 0.29-0.79) comparing the second with the lowest tertile (serum selenium concentration >82.40 microg/L). The adjusted OR for the highest tertile (serum selenium concentration >96.00 microg/L), was 0.30 (95% CI 0.17-0.52) (P-trend <0.001). An increase of 10 microg/L in serum selenium concentration was associated with a significant decreased bladder cancer risk (OR: 0.76; 95% CI 0.67-0.85). This case-control study suggests an inverse association between serum selenium concentration and bladder cancer risk.


Nucleotide sequence and expression of the Pseudomonas aeruginosa algF gene controlling acetylation of alginate.
Colonization of the cystic fibrosis lung by Pseudomonas aeruginosa is greatly facilitated by the production of an exopolysaccharide called alginate. In this study we determined the nucleotide sequence of an alginate modification gene, algF, which controls the addition of acetyl groups to alginate. Expression of algF using a T7 promoter-expression system showed that algF codes for a 24.5 kDa polypeptide (predicted size 22,832 Da) that is processed to 19.5 kDa. The N-terminus of the processed polypeptide matched the predicted amino acid sequence of AlgF starting at Asp-29. An algF mutant failed to produce alginate owing to a polar effect on the downstream algA gene. Although the algA gene, provided in trans, restored synthesis of alginate, the alginate was non-acetylated. We show that a plasmid containing both the algF and algA gene complements the alginate acetylation defect of the algF mutant strain.


Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM).
The inability to generate mesenchymal stromal cells (MSCs) of consistent potency likely is responsible for inconsistent clinical outcomes of patients with aGvHD receiving MSC products. We developed a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses, referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of the 69 patients who have received MSC-FFM. These were 51 children and 18 adults with refractory aGvHD grade II (4%), III (36%) or IV (59%). Patients were refractory either to frontline therapy (steroids) (29%) or to steroids and 1-5 additional lines of immunosuppressants (71%) were given infusions in four weekly intervals. The day 28 overall response rate was 83%; at the last follow-up, 61% and 25% of patients were in complete or partial remission. The median follow-up was 8.1 months. Six-month estimate for cumulative incidence of non-relapse mortality was 27% (range, 16-38); leukemia relapse mortality was 2% (range, 0-5). This was associated with a superior six-month overall survival (OS) probability rate of 71% (range, 61-83), compared to the outcome of patients not treated with MSC-FFM. This novel product was effective in children and adults, suggesting that MSC-FFM represents a promising therapy for steroid refractory aGvHD.


Iridium(III) silyl alkyl and iridacyclic compounds supported by 4,4'-di-tert-butyl-2,2'-bipyridyl.
Treatment of IrCl(3)x H(2)O with one equivalent of 4,4'-di-tert-butyl-2,2'-bipyridyl (dtbpy) in N,N-dimethylformamide (dmf) afforded [IrCl(3)(dmf)(dtbpy)] (1). Alkylation of 1 with Me(3)SiCH(2)MgCl resulted in C--Si cleavage of the Me(3)SiCH(2) group and formation of the Ir(III) silyl dialkyl compound [Ir(CH(2)SiMe(3))(dtbpy)(Me)(SiMe(3))] (2), which reacted with tBuNC to afford [Ir(tBuNC)(CH(2)SiMe(3))(dtbpy)(Me)(SiMe(3))] ([2(tBuNC)]). Reaction of 2 with phenylacetylene afforded dimeric [{Ir(C[triple chemical bond]CPh)(dtbpy)(SiMe(3))}(2)(mu-C[triple chemical bond]CPh)(2)] (3), in which the bridging PhC[triple chemical bond]C(-) ligands are bound to Ir in a mu-sigma:pi fashion. Alkylation of 1 with PhMe(2)CCH(2)MgCl afforded the cyclometalated compound [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4))(2-C(6)H(4)CMe(3))] (4), which features an agostic interaction between the Ir center and the 2-tert-butylphenyl ligand. The cyclic voltammogram of 4 in CH(2)Cl(2) shows a reversible Ir(IV)-Ir(III) couple at about 0.02 V versus ferrocenium/ferrocene. Oxidation of 4 in CH(2)Cl(2) with silver triflate afforded an Ir(IV) species that exhibits an anisotropic electron paramagnetic resonance (EPR) signal in CH(2)Cl(2) glass at 4 K with g( parallel)=2.430 and g( perpendicular)=2.110. Protonation of 4 with HCl and p-toluenesulfonic acid (HOTs) afforded [{Ir(dtbpy)(CH(2)CMe(2)Ph)Cl}(2)(mu-Cl)(2)] (5) and [Ir(dtbpy)(CH(2)CMe(2)Ph)(OTs)(2)] (6), respectively. Reaction of 5 with Li[BEt(3)H] gave the cyclometalated complex [{Ir(dtbpy)(CH(2)CMe(2)C(6)H(4))}(2)(mu-Cl)(2)] (7). Reaction of 4 with tetracyanoethylene in refluxing toluene resulted in electrophilic substitution of the iridacycle by C(2)(CN)(3) with formation of [Ir(dtbpy)(CH(2)CMe(2)C(6)H(3){4-C(2)(CN)(3)})(2-C(6)H(4)CMe(3))] (8). Reaction of 4 with diethyl maleate in refluxing toluene gave the iridafuran compound [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4)){kappa(2)(C,O)-C(CO(2)Et)CH(CO(2)Et)}] (9). Treatment of 9 with 2,6-dimethylphenyl isocyanide (xylNC) led to cleavage of the iridafuran ring and formation of [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4)){C(CO(2)Et)CH(CO(2)Et)}(xylNC)] (10). Protonation of 9 with HBF(4) afforded the dinuclear neophyl complex [(Ir(dtbpy)(CH(2)CMe(2)Ph){kappa(2)(C,O)-C(CO(2)Et)CH(CO(2)Et)})(2)][BF(4)](2) (11). The solid-state structures of complexes 2-5 and 8-11 have been determined.


Redundancy and complexity of information in cognitive performances of schizophrenic and normal individuals.
Examined cognitive performance of schizophrenic and normal Ss matched on age, education, and intelligence (N = 120). Complexity of information and redundant cues were manipulated systematically in a concept identification (CI) task. Schizophrenics were not impaired compared to normals in solution of problems with low redundancy. Whereas normals' performance was facilitated by redundant information, schizophrenics demonstrated marked deficit in CI as a function of that information. Results were interpreted in terms of schizophrenics' inability to filter out irrelevant information, in addition to their deficit in channel capacity for utilizing relevant-redundant cues, which have been shown to reliably facilitate normals' CI.


Rare Concurrence of Congenital Muscular Torticollis and a Malignant Tumor in the Same Sternocleidomastoid Muscle.
While congenital muscular torticollis (CMT) can occur along with other conditions, such as clavicle fracture or brachial plexus injury, these conditions exist outside the sternocleidomastoid muscle (SCM). We present a rare case with concurrence of CMT and a malignant tumor inside the same SCM, along with serial clinical and radiological findings of the atypical features of CMT. The malignant tumor was in fact a low-grade fibromyxoid sarcoma. To the best of our knowledge, the current case is the first of a concurrent condition of CMT inside the SCM. This case suggests that concurrent conditions could exist either inside or outside the SCM with CMT. Therefore, a thorough evaluation of SCM is required when subjects with CMT display atypical features, such as the increase of mass or poor response to conservative therapy. In that case, appropriate imaging modalities, such as ultrasonogram or magnetic resonance imaging, are useful for differential diagnosis.


Cardiovascular Screening before Sports Participation: Results of 11487 Children.
In this study, it is aimed to analyze the data of children who were referred to our clinic for pre-participation sports screening. Data, between September 2017 and December 2021, had been analyzed. All these subjects had been questioned for their personal and family medical stories and examined for cardiovascular system findings. Electrocardiography (ECG) and echocardiography were applied to all of them. 11487 children were consulted to the cardiology clinic for pre-sports participation screening. The mean age was 12.7±4,57 (7-18 years). 34/11487(0,29%) subjects weren't allowed to participate in sports activities at first. In 23 of 34 subjects, cardiac arrhythmias were established. 15 had Wolff-Parkinson-White (WPW) syndrome, 3 subjects had ventricular extrasystole, and also ventricular tachycardia in one of them. Four subjects had long QT syndrome and one had ST elevation with the pre-diagnosis of coronary artery disease. ECG screening alone aided in identifying asymptomatic (0.05%) that could have been potentially at risk for sudden cardiac death. Positive ECG and echocardiography findings involve a very little ratio.But ECG involves an important tool for screening lethal cardiac arrhythmias in asymptomatic patients.If ECG or echocardiography couldn't be taken, further evaluation should be necessary with symptoms and/or family history.


"Mean mugging": an exploration of young Aboriginal women's experiences of bullying in team sports.
Bullying among youth is rampant and research suggests that young Aboriginal women may be particularly susceptible to bullying. Sport participation has been identified as a possible mechanism to prevent bullying behaviors, yet few researchers have explored bullying within the context of sport. The purpose of this qualitative description study was to explore young Aboriginal women's experiences of bullying in team sports. Eight young Aboriginal women participated in one-on-one semistructured interviews and follow-up phone interviews. Data were analyzed using a content analysis, and findings were represented by five themes: (1) mean mugging, (2) sport specific, (3) happens all the time, (4) team bonding to address bullying, and (5) prevention through active coaches. The detailed descriptions shared by participants provide insight into a broad range of bullying experiences and serve as a foundation for addressing the bullying that occurs in sport.


All-in-focus fine needle aspiration biopsy imaging based on Fourier ptychographic microscopy.
Cytology is the study of whole cells in diagnostic pathology. Unlike standard histologic thinly sliced specimens, cytologic preparations consist of preparations of whole cells where cells commonly cluster and aggregate. As such, cytology preparations are generally much thicker than histologic slides, resulting in large patches of defocus when examined under the microscope. A diagnostic aggregate of cells often cannot be viewed in focus together, requiring pathologists to continually manipulate the focal plane, complicating the task of accurately assessing the entire cellular aggregate and thus in making a diagnosis. Further, it is extremely difficult to acquire useful uniformly in-focus digital images of cytology preparations for applications such as remote diagnostic evaluations and artificial intelligence models. The predominant current method to address this issue is to acquire digital images at multiple focal planes of the entire slide, which demands long scanning time, complex and expensive scanning systems, and huge storage capacity. Here we report a unique imaging method that can acquire cytologic images efficiently and computationally render all-in-focus digital images that are highly compact. This method applies a metric-based digital refocusing to microscopy data collected with a Fourier ptychographic microscope (FPM). The digitally refocused patches of images are then synthesized into an all-in-focus image. We report all-in-focus FPM results of thyroid fine needle aspiration (FNA) cytology samples, demonstrating our method's ability to overcome the height variance of 30 μm caused by cell aggregation, and rendering images at high resolution (corresponds to a standard microscope with objective NA of 0.75) and that are all-in-focus. This technology is applicable to standard microscopes, and we believe can have an impact on diagnostic accuracy as well as ease and speed of diagnosing challenging specimens. While we focus on cytology slides here, we anticipate this technology's advantages will translate well for histology applications. This technique also addresses the issue of remote rapid evaluation of cytology preparations. Finally, we believe that by resolving the focus heterogeneity issues in standard digital images, this technique is a critical advance for applying machine learning to cytology specimens.


[Circulating immune complexes in the serum of tumor patients].
The conditions for the detection of circulating immune complexes (CIC) were established by combination of polyethylene glycol precipitation with a nephelometric determination on the precipitate of endogenous C1q. The CIC precipitated from the sera of patients with breast carcinoma, malignant melanoma or autoimmune diseases were dissociated in SDS-beta-mercaptoethanol buffer and no differences were observed in the electrophoretic patterns os polyacrylamide gels allowing to characterize tumour specific antigens.


Improvements in outcomes in methadone patients on probation/parole regardless of counseling early in treatment.
This secondary data analysis examined the association between criminal justice (CJ) status and outcomes over 12 months of methadone maintenance treatment. In the parent study, 230 newly admitted patients were randomly assigned to methadone either with or without counseling for 4 months followed by standard methadone with counseling. Participants completed the ASI and urine drug testing at baseline and 4- and 12-month follow-up and the Treatment Readiness (TR) scale at baseline. The relationship between baseline CJ status (whether participants were on probation or parole), CJ status by study counseling condition, and CJ status by TR with heroin and cocaine use, illegal activity, days in treatment and treatment retention, arrests, and the number of days incarcerated or hospitalized during follow-up was examined. Compared with participants not on probation/parole, probationers/parolees showed significant reductions in cocaine-positive tests from baseline to 12 months (P < 0.001). Probationers/parolees additionally reported significantly fewer days of illegal activity than nonprobationers/parolees at 12 months (P = 0.02). There was no relationship between CJ status and counseling condition for any outcomes. The relationship between CJ status and TR was significant only for cocaine-positive tests assessed over time (P = 0.017). Findings suggest that methadone participants on probation/parole showed improvements in outcomes in comparison with participants not on probation/parole, regardless of whether they received counseling during the first 4 months of treatment.


Purification of a high molecular weight form of epidermal growth factor from urine of breast cancer patients.
A high molecular weight form of epidermal growth factor (EGF) was detected by means of an EGF radio-receptor assay and an anchorage-independent growth assay in the urine of breast cancer patients. Preliminary data indicate that the activity of this growth factor is associated with lymph node status and tumor size and that the activity becomes reduced after removal of the primary tumor. The EGF-related polypeptide was purified to homogeneity by a combination of Sephadex G-25 and Bio Gel P-30 chromatography followed by binding to, and elution from, EGF receptor rich A431 cells. Final purification was achieved after isoelectric focusing by following the biological activity of eluted polypeptides. A polypeptide of a pI of 3.4 was identified to carry EGF-like activity. This polypeptide migrated as a single band of 43 kDa in SDS-PAGE. Its biological activity was neutralized by a specific anti-hEGF-antibody indicating an immunological relationship with hEGF.


Psychosis and migration: does a correlation exist?
The mental health of migrants is considered today one of the major problems of individual and public health. Unlike other European countries, such as England and France, where migration is linked to a colonial past, Italy has only recently found itself faced with a tumultuous transformation of identity, becoming from a country of emigration, an immigration country. In light of all this, this work stems from the need to shed light on the relationship between social integration and development of psychiatric disorders in migrants, with particular attention to the correlation between migration and psychotic pathology. Finally, the elaboration of various issues related to the migration process will be dealt with, placing the priority on investigating the greater psychiatric morbidity in migrants compared with natives.


Formation of intramuscular connective tissue network in fish: first insight from the rainbow trout (Oncorhynchus mykiss).
The formation of the intramuscular connective tissue was investigated in rainbow trout Oncorhynchus mykiss by combining histological and in situ gene-expression analysis. Laminin, a primary component of basement membranes, surrounded superficial slow and deep fast muscle fibres in O. mykiss as soon as the hatching stage (c. 30 days post fertilization (dpf)). In contrast, type I collagen, the primary fibrillar collagen in muscle of vertebrates, appeared at the surface of individual slow and fast muscle fibres only at c. 90 and 110 dpf, respectively. The deposition of type I collagen in laminin-rich endomysium ensheathing individual muscle fibres correlated with the late appearance of collagen type 1 α 1 chain (col1α1) expressing fibroblasts inside slow and then fast-muscle masses. Double in situ hybridization indicated that coll1α1 expressing muscle resident fibroblasts also expressed collagen type 5 α 2 chain (col5α2) transcripts, showing that these cells are a major cellular source of fibrillar collagens within O. mykiss muscle. At c. 140 dpf, the formation of perimysium-like structure was manifested by the increase of type I collagen deposition around bundles of myofibres concomitantly with the alignment and elongation of some collagen-expressing fibroblasts. Overall, this study shows that the formation of O. mykiss intramuscular connective tissue network is completed only in aged fry when fibroblast-like cells expressing type I and V collagens arise inside of the growing myotome.


Systematic analysis of Long non-coding RNAs reveals diagnostic biomarkers and potential therapeutic drugs for intervertebral disc degeneration.
Long non-coding RNAs (lncRNAs) are related to a variety of human diseases. However, little is known about the role of lncRNA in intervertebral disc degeneration (IDD). LncRNA expression profile of human IDD were downloaded from Gene Expression Omnibus (GEO) database. Potential biomarkers and therapeutic drugs for IDD were analyzed by weighted gene co-expression network analysis (WGCNA), R software package Limma, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We identified 1455 differentially expressed genes and 423 differentially expressed lncRNAs. Twenty-six co-expression modules were obtained, among them, the tan, brown, and turquoise modules were most closely related to IDD. The turquoise module contained a large number of differential expressed lncRNAs and genes, these genes were mainly enriched in the MAPK signaling pathway, TGF-beta signaling pathway. Furthermore, we obtained 11,857 LmiRM-Degenerated, these lncRNAs and genes showed higher differential expression multiples and higher expression correlation. After constructing a disease-gene interaction network, 25 disease-specific genes and 9 disease-specific lncRNAs were identified. Combined with the drug-target gene interaction network, three drugs, namely, Calcium citrate, Calcium Phosphate, and Calcium phosphate dihydrate, which may have curative effects on IDD, were determined. Finally, a genetic diagnosis model and lncRNA diagnosis model with 100% diagnostic performance in both the training data set and the validation data set were established based on these genes and lncRNA. This study provided new diagnostic features for IDD and could help design personalized treatment of IDD.


A retrospective comparative study of aortic valve replacement with St. Jude medical and medtronic-hall prostheses: a 20-year follow-up study.
To compare the long-term clinical outcome of patients who underwent aortic valve replacement with St. Jude Medical and Medtronic-Hall mechanical prostheses. From June 1978 to June 1982, 43 Medtronic-Hall and 48 St. Jude Medical mechanical valves were implanted in 90 consecutive patients with aortic valve disease, and their clinical outcome was retrospectively assessed. At 20 years in the St. Jude Medical group and in the Medtronic-Hall group the actuarial rates of overall survival were 50 and 49% (p = NS), of cardiovascular survival 66 and 63% (p = NS), of valve-related survival 95 and 91% (p = NS), of freedom from major valve-related complications 83 and 45% (p = 0.005), from major cerebrovascular events 93 and 71% (p =0.06), from valve thrombosis 97 and 89% (p = NS), from aortic valve reoperation 93 and 88% (p = NS), from major bleeding 96 and 82% (p = 0.04), and from endocarditis 93 and 82% (p = NS), respectively. The linearized rate of overall major aortic valve prosthesis-related complications was 3.47%/year in the Medtronic-Hall valve group and 1.53%/year in the St. Jude Medical valve group (p = 0.003). Multivariate analysis showed that the type of prosthesis was predictive of freedom from valve-related complications (p = 0.01; 2.849; C.I. 95%: 1.246-6.516). The aortic St. Jude Medical mechanical valve seems to be associated with a slightly lower rate of long-term valve-related morbidity than the aortic Medtronic-Hall mechanical valve. Because of the small patient population and the retrospective nature of the study, the choice between these two prostheses should not be made only on the basis of these findings. However, these results suggest a reappraisal for further comparative studies with such an extended follow-up.


Trends in cholesterol screening and awareness of high blood cholesterol--United States, 1991-2003.
High blood cholesterol (HBC) (i.e., total cholesterol > or =240 mg/dL) is a major risk factor for heart disease, the leading cause of death in the United States. As a result, public health agencies and their partners have attempted to reduce the prevalence of HBC through screening and by increasing public awareness of HBC and strategies for reducing it. A national health objectives of Healthy People 2010 is to increase to 80% the proportion of adults aged > or =20 years who have been screened for HBC within the preceding 5 years. For this report, data from the Behavioral Risk Factor Surveillance System (BRFSS) collected during 1991-2003 were analyzed to examine trends in the percentage of adults screened for HBC and the percentage of those screened who were told they had HBC. The findings indicated that both percentages increased during 1991-2003 but that few states had achieved the national health objective for screening. Further emphasis on cholesterol screening is needed, particularly among Hispanic and Asian/Pacific Islander populations and young adults.


Hybrid spiral scanning in a double-clad fiber-based handheld confocal scanning light ophthalmoscope.
High-speed, accessible, and robust in vivo imaging of the human retina is critical for screening of retinal pathologies, such as diabetic retinopathy, age-related macular degeneration, and others. Scanning light ophthalmoscopy (SLO) is a retinal imaging modality that produces digital, en face images of the human retina with superior image gradability rates when compared to the current standard of care in screening for these diseases, namely the flood-illumination handheld fundus camera (HFC). However, current-generation commercial SLO systems are mostly tabletop devices, limiting their accessibility and utility in screening applications. Moreover, most existing SLO systems use raster scan patterns, which are both inefficient and lead to undesired subject gaze drift when used with visible or pseudo-visible illumination. Non-raster scan patterns, especially spiral scanning as described herein, promise advantages in both scan efficiency and reduced subject eye motion. In this work, we introduce a novel "hybrid spiral" scan pattern and the associated hardware design and real-time image reconstruction techniques necessary for its implementation in an SLO system. Building upon this core hybrid spiral scanning SLO (HSS-SLO) technology, we go on to present a complete handheld HSS-SLO system, featuring a fiber-coupled portable patient interface which leverages a dual-clad fiber (DCF) to form a single-path optical topology, thus ensuring mechanically robust co-alignment of illumination and collection apertures, a necessity for a handheld system. The feasibility of HSS-SLO for handheld, in vivo imaging is demonstrated by imaging eight human volunteers.


The brain and its time: intrinsic neural timescales are key for input processing.
We process and integrate multiple timescales into one meaningful whole. Recent evidence suggests that the brain displays a complex multiscale temporal organization. Different regions exhibit different timescales as described by the concept of intrinsic neural timescales (INT); however, their function and neural mechanisms remains unclear. We review recent literature on INT and propose that they are key for input processing. Specifically, they are shared across different species, i.e., input sharing. This suggests a role of INT in encoding inputs through matching the inputs' stochastics with the ongoing temporal statistics of the brain's neural activity, i.e., input encoding. Following simulation and empirical data, we point out input integration versus segregation and input sampling as key temporal mechanisms of input processing. This deeply grounds the brain within its environmental and evolutionary context. It carries major implications in understanding mental features and psychiatric disorders, as well as going beyond the brain in integrating timescales into artificial intelligence.


Sinonasal NUT carcinoma: A retrospective case series from a single institution.
Nuclear protein in testis (NUT) carcinoma is a rare, aggressive tumor defined by the presence of NUT gene rearrangement. The aim of this study was to describe the clinical, radiologic, and biological features of sinonasal NUT carcinoma. We retrospectively investigated NUT expression with clinicopathologic features in 145 cases with sinonasal malignancies diagnosed from January 2017 to December 2021 and reviewed the reported cases. Three (3/145, 2.07%) cases showed strong nuclear expression for NUT immunohistochemical, including one male and two females with ages from 37 to 57 years (mean, 45.33 years). All three cases involved the nasal cavity and sinuses; one of them involved the orbit and intracranial area. Histologically, all subjects showed poorly differentiated, small round cell morphology with distinct nuclei. All patients received surgery and chemoradiotherapy. One patient died of the disease 13 months after diagnosis, and two survived 12 and 15 months, respectively, without evidence of tumor recurrence. 51 cases of sinonasal NUT carcinoma (mean age 40.96 years) have been described to date. Among them, 28 are male, and 23 are female. Most cases expressed p63, AE1/AE3, as well as p40. NUT carcinoma is a rare and aggressive disease with a poor prognosis. It is crucial to perform NUT rearrangement-related tests for differential diagnosis of poorly differentiated/undifferentiated tumors in the nasal cavity and sinuses.


VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription.
The Vitamin D Receptor (VDR) is a member of the nuclear receptor superfamily and is of therapeutic interest in cancer and other settings. Regulation of microRNA (miRNA) by the VDR appears to be important to mediate its actions, for example, to control cell growth. To identify if and to what extent VDR-regulated miRNA patterns change in prostate cancer progression, we undertook miRNA microarray analyses in 7 cell models representing non-malignant and malignant prostate cells (RWPE-1, RWPE-2, HPr1, HPr1AR, LNCaP, LNCaP-C4-2, and PC-3). To focus on primary VDR regulatory events, we undertook expression analyses after 30 minutes treatment with 1α,25(OH)2D3. Across all models, 111 miRNAs were significantly modulated by 1α,25(OH)2D3 treatment. Of these, only 5 miRNAs were modulated in more than one cell model, and of these, only 3 miRNAs were modulated in the same direction. The patterns of miRNA regulation, and the networks they targeted, significantly distinguished the different cell types. Integration of 1α,25(OH)2D3-regulated miRNAs with published VDR ChIP-seq data showed significant enrichment of VDR peaks in flanking regions of miRNAs. Furthermore, mRNA and miRNA expression analyses in non-malignant RWPE-1 cells revealed patterns of miRNA and mRNA co-regulation; specifically, 13 significant reciprocal patterns were identified and these patterns were also observed in TCGA prostate cancer data. Lastly, motif search analysis revealed differential motif enrichment within VDR peaks flanking mRNA compared to miRNA genes. Together, this study revealed that miRNAs are rapidly regulated in a highly cell-type specific manner, and are significantly co-integrated with mRNA regulation.


The Improvement of Torsion Assessed by Cardiovascular Magnetic Resonance Feature Tracking after Coronary Artery Bypass Grafting: A Sensitive Index of Cardiac Function.
The aim of this study was to quantify left ventricular torsion by newly applied cardiovascular magnetic resonance feature tracking (CMR-FT), and to evaluate the clinical value of the ventricular torsion as a sensitive indicator of cardiac function by comparison of preoperative and postoperative torsion. A total of 54 volunteers and 36 patients with previous myocardial infarction (MI) and LV ejection fraction (EF) between 30%-50% were screened preoperatively or postoperatively by MRI. The patients' short axis views of the whole heart were acquired, and all patients had a scar area >75% in at least one of the anterior or inferior segments. Their apical and basal rotation values were analyzed by feature tracking, and the correlation analysis was performed for the improvement of LV torsion and ejection fraction after CABG. The intra- and inter-observer reliabilities of torsion measured by CMR-FT were assessed. In normal hearts, the apex rotated counterclockwise in the systolic period with the peak rotation as 10.2 ± 4.8°, and the base rotated clockwise as the peak value was 7.0 ± 3.3°. There was a timing hiatus between the apex and base untwisting, during which period the heart recoils and its suction sets the stage for the following rapid filling period. The postoperative torsion and rotation significantly improved compared with preoperative ones. However, the traditional indicator of cardiac function, ejection fraction, didn't show significant improvement. Left ventricular torsion derived from CMR-FT, which does not require specialized CMR sequences, was sensitive to patients with low ejection fraction whose cardiac function significantly improved after CABG. The rapid acquisition of this measurement has potential for the assessment of cardiac function in clinical practice.


Dynamic education of macrophages in different areas of human tumors.
Human tumor tissues can often be anatomically classified into areas of cancer nest, invading edge, and peritumoral stroma, each with distinct compositions and functional properties. Macrophages (Mφ) constitute a major component of the leukocyte infiltrate in tumors. These cells are derived from circulating monocytes, and in response to environmental signals, they exhibit distinct phenotypes with diverse functions. Soluble factors derived from cancer cells can alter the normal developmental process of Mφ that is intended to trigger transient early activation of monocytes in the peritumoral region, which in turn induces formation of suppressive Mφ in cancer nests. The activated monocytes in the peritumoral region attenuated the T-cell response by expressing B7-H1, and were superior to the suppressive tumor Mφ in inducing Th17 expansion, and thus repurpose the inflammatory response away from anti-tumor immunity (the sword) and towards tissue remodeling and proangiogenic pathways (a plowshare). In contrast, the suppressive Mφ can induce the production of Tregs in cancer nest. Accordingly, angiogenesis was most active at the invading edge, which was situated close to the peritumoral stroma with activated Mφ and the density of these activated monocytes is selectively associated with vascular invasion and metastasis in patients with hepatocellular carcinoma. These data reveal an intriguing mechanism in which human Th17 cells are generated and regulated by a fine-tuned collaborative action between different types of immune cells in distinct tumor microenvironments. These results give important new insights into the distinct role of macrophages in human tumor progression which would be helpful for the rational design of novel immune-based anticancer therapies.


Blocking of human immunodeficiency virus infection depends on cell density and viral stock age.
Quantitative infectivity assays were used to study how the blocking activity of soluble CD4 (sCD4) is affected by sCD4 concentration, target cell density, and viral stock age. During incubation with 20 nM sCD4, human immunodeficiency virus type 1 (HIV-1) stocks underwent irreversible inactivation. In contrast, inactivation with 2 nM sCD4 was almost entirely reversible. At lower sCD4 concentrations (less than or equal to 2 nM) and target cell densities of 6.25 x 10(4) ml-1, sCD4 blocking activity for HIV-1 gave a gp120-sCD4 association constant (Kassoc) of 1.7 x 10(9) M-1, which agrees with chemical measurements. At the higher density of 1.6 x 10(7) cells ml-1, however, the blocking activity was 20-fold less. During incubation of HIV-1 stock optimized for infectivity by rapid harvest, sCD4 blocking activity increased 20-fold during a 3-h window. These results show that competitive blocking activity depends strongly on target cell density and virion age. Thus, unappreciated variations in HIV stocks and assay conditions may hinder comparisons of blockers from laboratory to laboratory, and the age of HIV challenge stocks may influence studies of drug and vaccine efficacy. The results also suggest that blocking of viral particles in lymphoid compartments will require very high competitive blocker concentrations, which may explain the refractory outcomes from sCD4-based drug trials in humans.


Cyst of the septum pellucidum and Korsakoff's psychosis.
Noncommunicating cysts of the septum pelludicum are rare and diagnostic experience with CT scan is scanty. They may cause hydrocephalus because of obstruction of Monro's foramina. In this report we describe a young patient with acute Korsakoff's syndrome. The CT scan revealed a cyst of the septum pellucidum without hydrocephalus. Surgery disclosed a noncommunicating cyst compressing structures of the limbic system. After surgery symptoms disappeared.


Transcriptional regulation of podocyte specification and differentiation.
Glomerular visceral epithelial cells (podocytes) are highly specialized cells found in the vertebrate and invertebrate kidney and make up a major portion of the filtration barrier between blood and urinary spaces. During development, specification and differentiation of the podocyte lineage must be tightly orchestrated to produce highly specialized characteristics such as foot processes and slit diaphragms. Furthermore, podocytes are poised to direct incoming endothelial and mesangial cells during glomerular development. They express a number of growth factors that likely play a major role in these processes. Recent findings from transgenic and knockout mouse models and the identification of genes responsible for human podocyte disease have provided insight into transcriptional regulation of some of these processes. These transcription factors include Pax2, WT1 (the Wilms tumor suppressor gene), Pod1 (capsulin, epicardin), Kreisler (maf-1), lmx1b, and mf2. Furthermore, regulatory regions from a podocyte-restricted gene, NPHS1 (nephrin) that are required to direct podocyte-specific expression have been identified from both human and murine genes and provide a tool to further dissect the transcriptional regulation of podocyte-specific gene expression. This article reviews the present state of knowledge regarding transcriptional regulation of podocyte specification and differentiation.


Synthesis and applications of eco-magnetic nano-hydroxyapatite chitosan composite for enhanced fluoride sorption.
Adsorption is a significant reaction occurs between adsorbent/water interface for controlling the pollutants in the aqueous environment. In this regard, an eco-magnetic biosorbent was prepared by uniform deposition of magnetic Fe3O4 particles on the surface of nano-hydroxyapatite (n-HAp)/chitosan (CS) nanocomposite namely Fe3O4@n-HApCS composite as versatile sorbent for fluoride sorption. The resulting Fe3O4@n-HApCS nanocomposite was characterized by FTIR and SEM with EDAX techniques. The defluoridation capacity (DC) was found to depend on the contact time, pH, co-existing anions, initial fluoride concentration and temperature. The sorption isotherm was investigated by Freundlich, Langmuir and Temkin isotherm models using the batch method. The thermodynamic parameters revealed the feasibility, spontaneity and endothermic nature of fluoride sorption. The results of this research work designated that Fe3O4@n-HApCS composite having the excellent defluoridation capacity than the individual components and interesting to note that the easy magnetic separation of Fe3O4@n-HApCS composite from aqueous medium.


Cell-type-specific expression of alternatively spliced human fibronectin IIICS mRNAs.
Fibronectin polypeptide diversity is generated to a large extent by alternative splicing of the fibronectin primary transcript at three sites: two extra domain exons encoding extra structural repeats and a region of nonhomologous sequence termed the type-III connecting segment (IIICS). A novel double primer extension assay was developed to identify and quantify simultaneously each of the five human IIICS mRNA splicing variants. Expression of the five IIICS variants was analyzed in a variety of human normal and tumor cell types as well as in human liver. Differences in IIICS expression patterns were observed among different cell types, among fibroblasts of different tissue origins, and between comparable normal and transformed cells. The most predominant cell-type-specific differences were in the abundance of the one IIICS- mRNA variant relative to the four IIICS+ variants. The percentage of O variant (IIICS-) mRNAs within the total fibronectin mRNA pool varied between 3 and 17% among tumor cells and between 7 and 46% among normal cells. The O variant composed 57% of the fibronectin mRNA in liver tissue, correlating with the previously described increased abundance of IIICS- polypeptide subunits in plasma fibronectin, compared with those in cellular fibronectins. Additional cell-type-specific changes among the expression levels of the four IIICS+ mRNA variants are consistent with a proposed model in which regulation of an alternative selection of a 3'splice site predominates over regulation of the selection of a 5' splice site in generating specific patterns of IIICS mRNA expression.


[Newer immunosuppressive agents and their place in current practice].
The last decade has witnessed an expansion of the arsenal of new immunosuppressive agents to include several novel drugs and antibodies. The main indication of all these immunosuppressive agents is organ transplantation. In terms of its action, tacrolimus resembles cyclosporin A and is employed as the mainstay immunosuppressant or for what is referred to as rescue therapy in refractory rejection. Mycophenolate mofetil is an anti-metabolite replacing azathioprine in immunosuppressive protocols. Sirolimus is an agent for prophylactic use, either as part of a cyclosporin-based regimen to enhance the effect of cyclosporin or as an alternative of non-nephrotoxic immunosuppression to cyclosporin-based regimens; its indications are still being specified. Gusperimus could be used for anti-rejection therapy; however, it is not being used in this country as yet. Recently, two monoclonal antibodies against the IL-2 receptor, chimeric basiliximab and humanized daclizumab, have been employed. Both agents are of non-depletion type and are indicated for induction therapy in the early post-transplant period.


Influence of a Multiple Epoxy Chain Extender on the Rheological Behavior, Crystallization, and Mechanical Properties of Polyglycolic Acid.
This study investigated the impact of a multiple epoxy chain extender (ADR) on the rheological behavior, crystallization, and mechanical properties of polyglycolic acid (PGA). Tests of the torque and melt mass flow rate and dynamic rheological analysis were conducted to study the rheological behavior of PGA modified with ADR. The rheological results of the modified PGA showed a significantly increased viscosity and storage modulus with an increase in the ADR amount, which could be attributed to the chain extension/branching reactions between PGA and ADR. It was proved that ADR could be used as an efficient chain extender for tailoring the rheological performance of PGA. The Han plot of the modified PGA showed a transition of viscous behavior to elastic behavior, while the ADR content was increased from 0 to 0.9 phr. The formation of long-chain branches (LCBs) was confirmed via the Cole-Cole plot and weighted relaxation spectrum, wherein the LCBs substantially changed the rheological behavior of the modified PGA. The vGP plots predicted a star-type topological structure for the LCBs. The results of non-isothermal crystallization kinetics suggested that the crystallization of the modified PGA was predominantly homogeneous nucleation and three-dimensional growth. The crystallinity decreased slightly with the increase in the ADR amount. Compared to neat PGA, the modified PGA samples exhibited better tensile and flexural performances.


Idiopathic intracranial hypertension in a child with Bardet-Biedl syndrome.
Bardet-Biedl syndrome (BBS) is known to be associated with hydrocephalus, but not with idiopathic intracranial hypertension (IIH). Case presentation: We describe such a case and propose the pathogenesis. We also discuss the challenges of diagnosis, treatment, and monitoring outcomes in this population that is already at high risk of vision loss from retinal dystrophy. IIH can result from a combination of risk factors in conjunction with the underlying dysfunctional cilia in BBS patients. Monitoring disease progression is difficult, and as such IIH may be underdiagnosed or missed. Management must be adjusted to account for BBS patients' impaired metabolic and renal physiology. It is important that clinicians be aware of these challenges in this vulnerable population, and regular monitoring should be done to avoid preventable vision loss.


A National Emergency Airway Registry for children: landscape of tracheal intubation in 15 PICUs.
To characterize the landscape of process of care and safety outcomes for tracheal intubation across pediatric intensive care units Procedural process of care and safety outcomes of tracheal intubation across pediatric intensive care units has not been described. We hypothesize that the novel National Emergency Airway Registry for Children registry is a feasible tool to capture tracheal intubation process of care and outcomes. Prospective, descriptive. Fifteen academic PICUs in North America. Critically ill children requiring tracheal intubation in PICUs. Tracheal intubation quality improvement data were prospectively collected for all initial tracheal intubation in 15 PICUs from July 2010 to December 2011 using the National Emergency Airway Registry for Children tool with explicit site-specific compliance plans and operational definitions including adverse tracheal intubation associated events. One thousand seven hundred fifteen tracheal intubation encounters were reported (averaging 1/3.4 days, or 1/86 bed days). Ninety-eight percent of primary tracheal intubation were successful; 86% were successful with less than or equal to two attempts. First attempt was by pediatric residents in 23%, pediatric critical care fellows in 41%, and critical care attending physicians in 13%: first attempt success rate was 62%, first provider success rate was 79%. The first method was oral intubation in 1,659 (98%) and nasal in 55 (2%). Direct laryngoscopy was used in 96%. Ninety percent of tracheal intubation were with cuffed tracheal tubes. Adverse tracheal intubation associated events were reported in 20% of intubations (n = 372), with severe tracheal intubation associated events in 6% (n = 115). Esophageal intubation with immediate recognition was the most common tracheal intubation associated events (n = 167, 9%). History of difficult airway, diagnostic category, unstable hemodynamics, and resident provider as first airway provider were associated with occurrence of tracheal intubation associated events. Severe tracheal intubation associated events were associated with diagnostic category and pre-existing unstable hemodynamics. Elective tracheal intubation status was associated with fewer severe tracheal intubation associated events. National Emergency Airway Registry for Children was feasible to characterize PICU tracheal intubation procedural process of care and safety outcomes. Self-reported adverse tracheal intubation associated events occurred frequently and were associated with patient, provider, and practice characteristics.


A density-functional study for the liquid-vapor coexistence curve of nitrogen fluid.
We have used a density-functional theory based on the interaction site model to predict the liquid-vapor coexistence curve of nitrogen fluid. The pressure and chemical potential were calculated from thermodynamic integrations. The different paths of thermodynamic integration provide slightly different predictions for the liquid-vapor coexistence curve. However, these critical points and coexistence curves evaluated by the theory are in qualitative agreement with the experimental data. The theoretical coexistence curves scaled to critical constants agree with the experimental data quantitatively.


Engineering a humanized bone organ model in mice to study bone metastases.
Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM); however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.


Alpha 1-adrenergic receptor subtype determinants for 4-piperidyl oxazole antagonists.
Mutational studies in conjunction with ligand binding assays were used to examine the basis of alpha1-adrenergic receptor subtype selectivity for a series of 4-piperidyloxazole antagonists. A set of chimeric alpha 1A receptors were created by systematically substituting individual transmembrane domains from alpha 1D adrenergic receptors. The oxazole antagonists exhibited significant reductions in affinity against the receptor construct alpha 1A/D(TM2), and moderate reductions in affinity versus constructs alpha 1A/D(TM5), alpha 1A/B(TM5), and alpha 1A/D(TM6). Antagonist affinities for these chimeras exceeded those found for wild type alpha 1D and alpha 1B. Site-directed mutagenesis methods were then used to explore the role that individual residues in TM2 and TM5 play in ligand binding affinity and selectivity. These studies revealed that mutations at position 86 in the second transmembrane domain and position 185 in the fifth transmembrane domain of the alpha 1A receptor have a major impact on receptor subtype selectivity.


Context and the leadership experiences and perceptions of professionals: a review of the nursing profession.
Leadership studies which focus on categorising leadership styles have been critiqued for failure to consider the lived experience of leadership. The purpose of this paper is to use the framework of Jepson's model of contextual dynamics to explore whether this framework assists understanding of the "how and why" of lived leadership experience within the nursing profession. Themes for a purposeful literature search and review, having regard to the Jepson model, are drawn from the contemporary and dynamic context of nursing. Government reports, coupled with preliminary interviews with a nurseleadership team, guided selection of contextual issues. The contextual interactions arising from managerialism, existing hierarchical models of leadership and increasing knowledge work provided insights into leadership experience in nursing, in the contexts of professional identity and changing educational and generational profiles of nurses. The authors conclude that employing a contextual frame provides insights in studying leadership experience. The author propose additions to the cultural and institutional dimensions of Jepson's model. The findings have implications for structuring and communicating key roles and policies relevant to nursing leadership. These include the need to: address perceptions around the legitimacy of current nursing leaders to provide clinical leadership; modify hierarchical models of nursing leadership; address implications of the role of the knowledge workers. Observing nursing leadership through the lens of Jepson's model of contextual dynamics confirms that this is an important way of exploring how leadership is enacted. The authors found, however, the model also provided a useful frame for considering the experience and understanding of leadership by those to be led.


Size-dependent cellular uptake and TLR4 attenuation by gold nanoparticles in lung adenocarcinoma cells.
To elucidate uptake mechanisms and immunomodulatory potential of differently sized gold nanoparticles (GNPs) in lung adenocarcinoma cells (A549) to enable their use as an adjunct therapy for treating inflammation-linked lung cancer. Internalization of the synthesized (5, 15 and 30 nm) GNPs by various endocytosis pathways was determined. Immunomodulatory mechanisms induced by differently sized GNPs in A549 cells in the presence of TLR4 and TLR9 ligands were evaluated. GNPs were size-dependently internalized efficiently by A549 cells. Various sized GNPs downregulated the expression of proinflammatory signaling molecules (5 nm most potent). Mechanistically, 5-nm GNPs attenuated TLR4 signaling by downregulating TLR4 expression in A549 cells. Our study suggests the use of immunomodulatory GNPs as an adjunct therapy against inflammation-linked lung cancer.


The role of the MDM2/p53 axis in anti-tumor immune responses.
Mouse double minute 2 homolog (MDM2) is a negative regulator of the tumor suppressor p53 and often highly expressed in acute myeloid leukemia (AML) and different solid tumors. Inactivating mutations in TP53, the gene encoding for p53, confers an unfavorable prognosis in AML and increases the risk for relapse after allogeneic hematopoietic cell transplantation (allo-HCT). We review the concept that manipulation of MDM2 and p53 could enhance immunogenicity of AML and solid tumor cells. Additionally, we discuss the mechanisms by which MDM2 and p53 regulate MHC class I and II expression, transcription of dsRNA of endogenous retroviruses, interferon responses, IL-15 production and TRAIL-receptor 1 and 2 expression on malignant cells. The direct effects of MDM2-inhibition or MDM2 deletion in effector T cells are discussed in the context of cancer immunotherapy. The preclinical findings are connected to clinical studies using MDM2-inhibition to enhance anti-tumor immunity in patients. In aggregate, this review summarizes current evidence supporting the use of MDM2-inhibition to restore p53, as well as direct effects of MDM2-inhibition on T cells as an emerging concept for combined anti-tumor immunotherapy against hematological malignancies and beyond.