Sensitivity and specificity of an improved rapid latex agglutination test for identification of methicillin-sensitive and -resistant Staphylococcus aureus isolates.
The performance of a second-generation rapid agglutination kit, Slidex Staph Plus (SSP; bioMérieux), was compared to those of the Slidex Staph (SS; bioMérieux), Staphaurex (SRX; Murex Diagnostics), and BBL Staphyloslide (BBL; Becton Dickinson) kits by using 508 clinical isolates composed of 150 methicillin-sensitive Staphylococcus aureus (MSSA) organisms, 154 methicillin-resistant S. aureus (MRSA) organisms, and 204 non-S. aureus Staphylococcus spp. Of the 508 isolates tested, 75% were fresh clinical isolates, with the remainder taken from five different freezer collections. All four agglutination tests had comparable sensitivities for MSSA and MRSA. However, the SS kit was significantly less specific (93.1%) than the three other tests (P > 0.05, McNemar test). These results demonstrate that the new rapid latex agglutination kit, SSP, was more specific for the identification of S. aureus than the previous version and performed comparably to the SRX and BBL kits.


A phosphatidylserine binding site in factor Va C1 domain regulates both assembly and activity of the prothrombinase complex.
Tightly associated factor V(a) (FVa) and factor X(a) (FXa) serve as the essential prothrombin-activating complex that assembles on phosphatidylserine (PS)-containing platelet membranes during blood coagulation. We have previously shown that (1) a soluble form of PS (C6PS) triggers assembly of a fully active FVa-FXa complex in solution and (2) that 2 molecules of C6PS bind to FVa light chain with one occupying a site in the C2 domain. We expressed human factor V(a) (rFVa) with mutations in either the C1 domain (Y1956,L1957)A, the C2 domain (W2063,W2064)A, or both C domains (Y1956,L1957,W2063,W2064)A. Mutations in the C1 and C1-C2 domains of rFVa reduced the rate of activation of prothrombin to thrombin by FXa in the presence of 400 muM C6PS by 14 000- to 15 000-fold relative to either wild-type or C2 mutant factor rFVa. The K(d')s of FXa binding with rFVa (wild-type, C2 mutant, C1 mutant, and C1-C2 mutant) were 3, 4, 564, and 624 nM, respectively. Equilibrium dialysis experiments detected binding of 4, 3, and 2 molecules of C6PS to wild-type rFVa, C1-mutated, and C1,C2-mutated rFVa, respectively. Because FVa heavy chain binds 2 molecules of C6PS, we conclude that both C2 and C1 domains bind one C6PS, with binding to the C1 domain regulating prothrombinase complex assembly.


Maternal feeding styles in infancy predict child body mass index z-scores at 72 months: findings from a cohort of Jamaican children.
To explore whether maternal feeding styles at 12 months predict child Body Mass Index (BMI) z-scores at 72 months and evaluate whether BMI z-scores at 18 months mediates the association. Data from 239 mother-child pairs participating in a parenting intervention were analyzed. Feeding information was ascertained at 12 months by questionnaire with feeding styles identified using factor analysis. Children's weight and length/height were measured at 18 and 72 months and BMI z-scores computed. Maternal sociodemographic data, depressive symptoms and language skills were obtained by questionnaire. Multilevel linear regression analysis was used to examine whether feeding styles predicted 72 month BMI z-scores. Complete case analysis was conducted and multiple imputation used to treat missing values of explanatory and outcome variables at 18 and 72 months. Mediational analysis was performed to assess the indirect effects of feeding styles on 72 month BMI z-scores via 18 month BMI z-scores. Restrictive feeding at age 12 months predicted higher 72 month BMI z-scores in both complete case analysis [β (95%CI): 0.19 (0.02, 0.37)] and multiple imputation [β (95%CI): 0.20 (0.02, 0.39)]. Uninvolved, forceful, indulgent and responsive feeding styles were not significant predictors of 72 month BMI z-scores. A significant indirect effect was observed between restrictive feeding and child BMI z-scores at 72 months via 18 month BMI z-scores [β (95% CI) 0.12 (0.03, 0.22)]. Restrictive feeding at 12 months was associated with higher BMI z-scores at 72 months and appeared to be mediated by BMI z-scores at 18 months.


Stimulation of neutrophil production in CSF-1-responsive clones.
The hematopoietic growth factor CSF-1 has been considered relatively lineage specific for the production of macrophages, whereas GM-CSF elicits a predominance of neutrophils. It is likely that in vivo, individual clones are stimulated by the two CSFs, although the effect of dual stimulation on progenitors and their progeny has not been completely explored. We found that in cultures initiated with low concentrations of CSF-1 or GM-CSF, alone or in combination, production of macrophages predominated. Maximally stimulatory concentrations of CSF-1 elicited a predominance of macrophages, whereas maximal GM-CSF elicited many more neutrophil/macrophage colonies and pure neutrophil colonies. A combination of maximal CSF-1 and GM-CSF elicited the same differentiation as GM-CSF alone. Delayed addition of GM-CSF to cultures initiated with CSF-1 elicited colonies indistinguishable from GM-CSF alone, suggesting that neutrophil production had been switched on by GM-CSF. In mapping studies, colonies initiated by CSF-1 increased or switched on neutrophil production when GM-CSF was added as a second stimulus. These studies show that individual clones are responsive to both CSFs, and that the differentiating influence of GM-CSF predominates over that of CSF-1. In cultures to which only CSF-1 was added, a population of progenitors was sustained that produced neutrophils only after a GM-CSF stimulus. Thus, CSF-1 may participate in maintaining a reserve of progenitors for neutrophils during periods of increased neutrophil demand.


Elemental dysregulation in psychotic spectrum disorders: A review and research synthesis.
Accumulating evidence from observational studies, genetic research, and animal models suggests a relationship between toxic and nutritive elements and psychotic spectrum disorders (PSD). This review systematically evaluates the current research evidence for two hypotheses: 1) that exposures to abnormal levels of toxic and nutritive elements early in life contributes to the subsequent development of PSD, and 2) that an imbalance of element levels is linked to psychotic illness and clinical severity. We focused on the extant literature on five elements, lead (Pb), copper (Cu), magnesium (Mg), manganese (Mn), and zinc (Zn), because of their previously documented associations with psychiatric problems and the availability of pertinent literature. The review identified 38 studies of which 11 measured Pb, 27 measured Cu, 16 measured Mg, 15 measured Mn, and 25 measured Zn concentrations in PSD patients and controls. A majority of research has been conducted on nutritive element imbalance, and findings are largely mixed. While it is biologically plausible that element dysregulation is an important modifiable risk factor for PSD, more research into exposure in early life is needed to better characterize this relationship.


Lymphangiomyomatosis arising in the pelvic cavity: a case report.
Lymphangioleiomyomatosis (LAM) is a rare disease usually occurring in young women of child-bearing age. It is characterized by a distinctive proliferation of lymphatic smooth muscle cells, especially occurring in the pulmonary parenchyme. The majority of primary LAM occurs in the lung, but there are a few reports of extrapulmonary cases. We report a case of a 21-yr-old female who first complained of low abdominal pain and was referred from a local clinic with the impression of an ovarian cyst. Gynecologic ultrasonography revealed a large posterior pelvic mass with an irregular echogenicity measuring 9.7 x 4.2 cm in size. Pelviscopy showed a large, thin walled, partly cystic, pelvic mass. The mass was partly removed. Microscopically, the mass was characterized by a haphazard proliferation of smooth muscle cells arranged in fascicular, trabecular, and papillary patterns around a ramifying network of endothelium-lined spaces. The cells were plump or epithelioid with abundant eosinophilic cytoplasm and showed a positive reaction for both alpha-smooth muscle actin and HMB-45 antigen. Surgical and pathological findings were consistent with pelvic retroperitoneal LAM. Despite the numerous treatment attempts, the patient suffered from intractable chylous ascites and developed pulmonary LAM and died due to severe respiratory distress.


Thermal properties of bi nanowire arrays with different orientations and diameters.
The thermal properties of single-crystalline Bi nanowire arrays with different orientations and diameters were studied by differential scanning calorimeter and in situ high-temperature X-ray diffraction. Bi nanowires were fabricated by a pulsed electrodeposition technique within the porous anodic alumina membrane. The relationships between the orientation and diameter of Bi nanowires and the corresponding thermal properties are deduced solely from experimental results. It is shown that the melting point decreases with decreasing nanowire diameter, and there is an anisotropic thermal expansion property of Bi nanowires with different orientations and diameters. The transition of the thermal expansion coefficient from positive at low temperature to negative at high temperature for Bi nanowire arrays was analyzed and discussed.


Syntheses of polybrominated indoles from the red alga Laurencia brongniartii and the brittle star Ophiocoma erinaceus.
The red alga Laurencia brongniartii and brittle star Ophiocoma erinaceus metabolites 2,3,6-tribromo-1-methylindole (1) and 2,3,5,6-tetrabromo-1-methylindole (2) are easily synthesized selectively from 2,3-dibromo-1-methylindole (5), which in turn is prepared from indole (3) in one continuous sequence in 92% yield. Moreover, 2 can be made from both 1 and 5 in 67% and 65% yields, respectively.


Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL.
This study was designed to investigate the effects of prolonged activation of AMP-activated protein kinase (AMPK) on lipid partitioning and the potential molecular mechanisms involved in these processes in white adipose tissue (WAT). Rat epididymal adipocytes were incubated with 5'-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside (AICAR;0.5 mM) for 15 h. Also, epididymal adipocytes were isolated 15 h after AICAR was injected (i.p. 0.7 g/kg body weight) in rats. Adipocytes were utilized for various metabolic assays and for determination of gene expression and protein content. Time-dependent in vivo plasma NEFA concentrations were determined. AICAR treatment significantly increased AMPK activation, inhibited lipogenesis, and increased FA oxidation. This was accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR)alpha, PPARdelta, and PPARgamma-coactivator-1alpha (PGC-1alpha) mRNA levels. Lipolysis was first suppressed, but then increased, both in vitro and in vivo, with prolonged AICAR treatment. Exposure to AICAR increased adipose triglyceride lipase (ATGL) content and FA release, despite inhibition of basal and epinephrine-stimulated hormone-sensitive lipase (HSL) activity. Here, we provide evidence that prolonged AICAR-induced AMPK activation can remodel adipocyte metabolism by upregulating pathways that favor energy dissipation versus lipid storage in WAT. Additionally, we show novel time-dependent effects of AICAR-induced AMPK activation on lipolysis, which involves antagonistic modulation of HSL and ATGL.


Noise suppression properties of an interferometer-based regenerator for differential phase-shift keying data.
We studied the amplitude and phase noise suppression properties of an all-optical regenerator for differential phase-shift keying data. A detailed analytical investigation is performed and compared with numerical simulations for different working points. The results show that both amplitude and phase can be regenerated. However, simultaneous amplitude and phase noise suppression is possible only if the phase degradation is stronger than the amplitude degradation, for instance, due to nonlinear phase noise.


The views of teenagers with obesity, their caregivers, and doctors: a plain language summary of the ACTION Teens global survey.
This is a summary of a research survey called ACTION Teens. In our survey, 12,987 people from 10 countries answered questions about obesity. They were: 5275 teenagers with obesity, 5389 caregivers of teenagers with obesity, and 2323 doctors who provide medical care for teenagers with obesity. Most teenagers with obesity were worried about their weight and thought that losing weight was their responsibility. Many teenagers had already tried to lose weight. For teenagers, wanting to be more fit or in better shape was the top reason for wanting to lose weight. Some caregivers did not realize how worried their teenager was about their own weight. There were also some caregivers who were not aware of their teenager's recent attempts to lose weight. As a group, the doctors did not know the main reasons why teenagers want to lose weight. They also did not know the main reasons preventing teenagers from losing weight. Teenagers with obesity will be better supported and understood if there is better communication between teenagers, caregivers, and doctors. Clinical Trial Registration: NCT05013359 (ClinicalTrials.gov).


Reduction Of St Segment Elevation In Diabetic Patients With Myocardial Infarction After Thrombolytic Therapy.
Acute coronary artery disease (CAD) is one of the main causes of death in today's world. Myocardial infarction (MI) tends to be more common among diabetic patients. One of the most effective and used (in our settings) methods of resolution of MI is administration of streptokinase (SK). This study was conducted with the aim to determine the efficacy of thrombolytic therapy in reduction of ST segment elevation in acute MI patients presenting with diabetes. A descriptive case series with selection of 130 patients through nonprobability purposive sampling was conducted at the Medical Departments of Services Hospital Lahore. The study was completed in 6 Months. Patients 18-80 years of age having either gender diagnosed with confirmed acute myocardial infarction were included in this study. All patients were then injected with streptokinase 1.5 mu. Pre S and Post SK ECGs were done and ST segment elevation measured also measuring reduction of ST segment. The mean age of the patients was noted as 54.42±8.80 years. There were 62.31% males. Mean reduction in ST-segment elevation of the patients was noted as 58.53±26.01. The efficacy was achieved in 47.7% patients. It is concluded that SK can be effective in almost half of diabetic patients with myocardial infarction.


A simple correction for ties when censoring times depend on covariates.
We point out that the conventional methods for ties correction may be seriously biased when censoring times depend on covariates. A simple modification to the Efron correction method is suggested which works remarkably well in simulation studies. The method corresponds closely to breaking ties by random ordering. The modified correction method is easy to implement and computationally no more demanding than the Efron correction.


Chronic SARS-CoV-2, a Cause of Post-acute COVID-19 Sequelae (Long-COVID)?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause coronavirus disease 2019 (COVID-19). Most individuals recover from SARS-CoV-2 infection, however, many continue to experience a cluster of persistent symptoms for months following resolution of acute disease; a syndrome that has been named Long-COVID. While the biological cause, or causes, of Long-COVID have not yet been confirmed, the main proposals have centred around either virus-induced autoimmunity or virus-induced tissue dysfunction. However, an alternative suggestion that a latent chronic infection could be responsible for the symptoms of Long-COVID has received minimal attention despite recent findings that SARS-CoV-2 genetic material and infections are detected in some individuals months following resolution of respiratory disease. Here we discuss literature supporting the possibility that Long-COVID occurs as a result of chronic SARS-CoV-2 infections.


Provision of assistive technology devices among people with ALS in Germany: a platform-case management approach.
The procurement of assistive technology devices (ATD) is an essential component of managed care in ALS. The objective was to analyze the standards of care for ATD and to identify challenges in the provision process. A cohort study design was used. We investigated the provision of 11,364 ATD in 1494 patients with ALS at 12 ALS centers in Germany over four years. Participants were patients that entered a case management program for ATD including systematic assessment of ATD on a digital management platform. Wheelchairs (requested in 65% of patients), orthoses (52%), bathroom adaptations (49%), and communication devices (46%) were the most needed ATD. There was a wide range in the number of indicated ATD per patient: 1 to 4 ATD per patient in 45% of patients, 5 to 20 ATD in 48%, and >20 ATD in 7% of patients. Seventy percent of all requested ATD were effectively delivered. However, an alarming failure rate during procurement was found in ATD that are crucial for ALS patients such as powered wheelchairs (52%), communication devices (39%), or orthoses (21%). Leading causes for not providing ATD were the refusal by health insurances, the decision by patients, and the death of the patient before delivery of the device. The need for ATD was highly prevalent among ALS patients. Failed or protracted provision posed substantial barriers to ATD procurement. Targeted national strategies and the incorporation of ATD indication criteria in international ALS treatment guidelines are urgently needed to overcome these barriers.


Trade-off between reservoir yield and evaporation losses as a function of lake morphology in semi-arid Brazil.
This study investigates the relationships between yield and evaporation as a function of lake morphology in semi-arid Brazil. First, a new methodology was proposed to classify the morphology of 40 reservoirs in the Ceará State, with storage capacities ranging from approximately 5 to 4500 hm3. Then, Monte Carlo simulations were conducted to study the effect of reservoir morphology (including real and simplified conical forms) on the water storage process at different reliability levels. The reservoirs were categorized as convex (60.0%), slightly convex (27.5%) or linear (12.5%). When the conical approximation was used instead of the real lake form, a trade-off occurred between reservoir yield and evaporation losses, with different trends for the convex, slightly convex and linear reservoirs. Using the conical approximation, the water yield prediction errors reached approximately 5% of the mean annual inflow, which is negligible for large reservoirs. However, for smaller reservoirs, this error became important. Therefore, this paper presents a new procedure for correcting the yield-evaporation relationships that were obtained by assuming a conical approximation rather than the real reservoir morphology. The combination of this correction with the Regulation Triangle Diagram is useful for rapidly and objectively predicting reservoir yield and evaporation losses in semi-arid environments.


[Studies on the relation between late dumping syndrome and glucagon responses to glucose].
This study was planned in pursuit of the relation between glucagon responses to glucose and the late dumping syndrome. Clinically, 75 g oral glucose tolerance test to seven late dumpers, ten gastrectomized patients and ten normal subjects were performed. And experimentary, 20 ml 25% glucose was put into small intestinal blind loops prepared in dogs, which were made the jejunum region and then the ileum region. 1. The mean oral glucose tolerance curve in gastrectomized patients was oxyhyperglycemic, and this tendency was seen in late dumpers. But, for only late dumpers, the low blood glucose concentration which was under 50 mg/dl appeared within one and half to three hours after oral glucose load. 2. The change of serum IRI in gastrectomized patients displayed the initial hyperinsulinemia, that was similar in late dumpers. 3. Pancreatic glucagon (GI) levels were within normal limits in normal subjects and late dumpers, but were significantly increased in gastrectomized patients. 4. Enteroglucagon (gutGLI) levels were not so increased in normal subjects, but were significantly increased in gastrectomized patients and late dumpers as well. 5. GutGLI levels were increased only by putting into the ileum loop. But hypersecretion of gutGLI did not affect the blood glucose curve and the change of serum IRI significantly. These results described above suggest that the pathogenesis of the hypoglycemia in the late dumping syndrome may be responsible for no hypersecretion of GI, for some reason, to prevent hypoglycemia against hyperinsulinemia with oxyhyperglycemia, and that gutGLI may not play so important part in the regulation of the blood glucose level.


The One Minute Preceptor: A Vital Tool During COVID-19.
The One Minute Preceptor (OMP) model of teaching has an important role to play during the COVID-19 pandemic. It's quick and easy to learn and can be applied to any clinical setting. By responding directly to a student's needs, and building on the knowledge they already hold, the OMP is able to offer relevant and opportunistic teaching that the learner can immediately apply. Finally, the OMP can be taught in under two hours meaning medical staff not used to regularly teaching can develop the confidence to offer high quality educational interventions.


[Management of unexpected cancer in locally resected colorectal polyps].
Excised colorectal polyps may contain unexpected malignancy. Once diagnosed histologically, further management is controversial, and little evidence exists to help in the choice between salvage bowel resection, local resection, systemic oncological treatment or watchful waiting. Choice of treatment must take patient-related factors as age and co-morbidity into consideration. Clinicians often face a dilemma concerning further treatment because of the scarce evidence. We want to establish a suggestion of a tailor-made treatment of malignant colorectal polyps based on the given evidence.


Deprescribing: An Application to Medication Management in Older Adults.
Polypharmacy has been found to have potentially negative consequences for patients due to use of potentially inappropriate medications, as well as increased risk of drug interactions and adverse effects. Deprescribing has been proposed as a method of improving medication use throughout a patient's course of care. This article reviews the process of deprescribing and applies the process to medication classes commonly encountered by clinical pharmacists. This review of therapeutics included studies identified through a PubMed search and by review of the reference list of included studies. Relevant studies known to the author were also included. Previous studies have identified several classes of medications as a high priority for construction of evidence-based deprescribing guidelines. In the absence of currently available evidence-based clinical practice guidelines, this articles reviews applicable evidence and applies the deprescribing process to three high-priority medication classes: statins, cholinesterase inhibitors and bisphosphonates. Available evidence can be used to apply the deprescribing process to preventive medications for chronic diseases commonly encountered by clinical pharmacists.


Vascular selectivity of felodipine: clinical experience.
Felodipine is a new calcium antagonist with vascular selectivity. It has a high potency in arterial resistance vessels and no apparent action on capacitance vessels. It lacks significant effects on myocardial contractility and cardiac conduction. It is an effective antihypertensive agent and may be safely combined with beta-adrenoceptor blockade. This report outlines work confirming the vascular selectivity of felodipine by examining its clinical effects in hypertension, ischemic heart disease, and congestive heart failure.


[Interventions to promote social communication in children with autism spectrum disorders].
The difficulties encountered when it comes to social communication are one of the core disorders experienced by persons with autism spectrum disorders (ASD). This problem leads to feelings of loneliness and social exclusion, which negatively affect the quality of life. To review the characteristics of the main interventions in this field in high-functioning ASD. Strategies employed include social stories, comic-strip conversations or videomodelling, and interventions mediated by peers and multicomponent treatments. The design of the programmes used today has evolved towards more ecological approaches that take the family, teachers and companions into account in the treatment. The most recent literature reviews have found evidence of significant improvements following their implementation, which has been reflected in better social competence and lesser feelings of loneliness. The social communication intervention must combine individualised instruction with consideration of the child's environment and the motivation towards communicative interaction.


Characterization of colony morphology variants isolated from Streptococcus pneumoniae biofilms.
In this study, we report the isolation of colony morphology variants from Streptococcus pneumoniae serotype 3 biofilms. The colony variants differed in colony size (large, medium, and small) and their mucoid appearance on blood agar. The small nonmucoid variant (SCV) emerged during the initial attachment stage of S. pneumoniae biofilm formation and dominated over the course of biofilm growth. Mucoid variants appeared at later biofilm developmental stages. The reduction in colony size/mucoidy correlated with a decrease in capsule production and an increase in initial attachment. The large mucoid variant formed flat unstructured biofilms, failed to aggregate in liquid culture, and adhered poorly to solid surfaces. In contrast, SCVs autoaggregated in liquid culture, hyperadhered to solid surfaces, and formed biofilms with significant three-dimensional structure, mainly in the form of microcolonies. The variants showed similar antibiotic resistance/susceptibility based on a modified Kirby-Bauer test and when grown as biofilms. However, antimicrobial treatment of S. pneumoniae biofilms altered the colony variant's distribution and mainly affected the most interior areas of biofilm microcolonies. To further explore the nature of the variants, the capsule biosynthetic operon (cps3DSUM) was explored in greater detail. The genetic analysis indicated that the emergence of nonmucoid variants was due to a deletion comprising cps3DSU as well as additional genes upstream of the cps3 operon. Overall, our findings suggest that in vitro biofilm formation of S. pneumoniae serotype 3 coincides with the emergence of colony variants with distinct genotypic and phenotypic characteristics.


Feasibility of cardiac resynchronization therapy in a patient with complex congenital heart disease and dextrocardia, facilitated by cardiac computed tomography and coronary sinus venography.
We describe a case with pacemaker implantation for cardiac resynchronization therapy (CRT) in a patient with complex congenital heart disease, facilitated by cardiac computed tomography (CT) and coronary sinus (CS) venography. A 37-year-old male presented with congenitally corrected transposition of the great arteries and mesocardia, along with a history of two open heart surgeries (closure of atrial septal defects and a ventricular septal defect, and pulmonary valvectomy at age 7; mechanical tricuspid valve replacement at age 13). He showed symptoms of progressive heart failure (NYHA class III) with significant impairment of the systemic right ventricular function. He also developed permanent atrial fibrillation with a junctional rhythm at a rate of 45 beats per minute. Biventricular pacing without an atrial lead was considered to be the best option available. CRT implantation was facilitated by proper identification of CS anatomy utilizing cardiac CT and CS venography and was performed without any complications. At follow up, a postero-anterior chest X-ray showed the final position of the right-sided ventricular (left ventricular morphology) lead pointing to the apex and the left ventricular lead at the posterolateral aspect of the systemic ventricle (right ventricular morphology).


[Hormonal disturbances in men with a prostatic adenoma (author's transl)].
On the basis of a series of hormone estimations in elderly men with a prostatic adenoma, and in men not suffering from the condition (old or young), the authors attempt to develop a physiopathological theory of the pathogenesis of prostatic adenoma. The elderly subject not suffering from a prostatic adenoma has lower blood testosterone, DHT (dihydrotestosterone), LH, FSH and oestrogen levels than the elderly subject with an adenoma, whilst the latter has a lower serum progesterone level. In patients with an adenoma, all the urinary metabolites of testosterone are excreted at markedly higher levels than normal. After prostatectomy, mean serum testosterone and DHT levels fall. In patients undergoing surgery for prostatic adenoma there is a higher level of testosterone and DHT in prostatic venous blood than in the peripheral blood. In prostatic adenoma sufferers, the injection of LHRH results in a higher secretion of LH and FSH than in the control group, but this phenomenon caused an increase in testosterone level only in the controls and not in the adenoma patients. Finally, in all patients with a prostatic adenoma in the absence of stimulation by LHRH, blood testosterone levels were proportional to LH levels. Pathogenic hypothesis: the initial phenomenon could be testicular atrophy in the elderly resulting in the active secretion of gonadotrophins, which themselves would cause a hypersecretion of testosterone and its derivatives within the prostatic tissue itself. It remains to obtain evidence of the existence of gonadotrophins receptor in the prostate, the insensitivity of testicular tissue in the elderly subject to increased gonadotrophin levels and the reasons for which the increased secretion of testosterone by adenomatous prostatic tissue does not in its turn induce inhibition of pituitary hypersecretion of gonadotrophins.


Prevalence and Severity of Dermatological Condition-Associated Skin Pain in the Chinese.
Although the characteristics of cutaneous sensory symptoms in the general population have been documented, dermatological condition-associated skin pain has not been characterized yet. In the present study, we aimed to characterize dermatological condition-associated skin pain in the Chinese. A questionnaire was given to outpatients to identify self-proclaimed skin pain at our dermatology clinic. The severity of skin pain was assessed using pain scale 0-10. Prevalence and pain severity were compared between males and females. A total of 2144 patients, including 1254 females and 890 males aged 13-94 years, were included in this study. The overall prevalence of skin pain was 9.93% in this cohort. The prevalence of skin pain varied greatly with dermatological conditions (p<0.0001). Moreover, a higher prevalence of skin pain was observed in males than in females (p<0.05). Among the dermatological conditions reported, higher skin pain scales were found in subjects with either glucocorticoid-induced dermatitis (4.20 ± 0.73) or herpes zoster (4.00 ± 0.29). While the overall pain scales were comparable between males and females (2.38 ± 0.13 versus 2.68 ± 0.13), pain scales in patients with eczematous dermatitis were higher in females than in males (p<0.05). Furthermore, pain scales correlated positively with age. However, pain scales did not differ between subjects with versus without a family history of cutaneous sensory symptoms. These results demonstrate that the prevalence and severity of dermatological condition-associated skin pain vary with dermatological conditions and gender in the Chinese. Patients with some dermatological conditions may experience skin pain. Although the pain is moderate, it can negatively impact the quality of patients' lives. Alleviation of skin pain should be considered when treating patients with certain dermatological conditions.


CT-guided transthoracic needle biopsy using a puncture site-down positioning technique.
We have developed a new CT-guided technique using puncture site-down positioning during the biopsy. The goal of our study was to determine the efficacy and safety of this technique for biopsy of lung lesions compared with the standard technique. Medical records of 236 patients who underwent CT-guided transthoracic needle biopsy were retrospectively evaluated. This study included 89 cases that were biopsied using the standard technique (group A) and 147 cases that were biopsied using the puncture site-down positioning technique (group B). A 20-gauge automated cutting needle without coaxial technique was used in all patients. Medical records were reviewed for lesion size and location, biopsy results, and complications. When using the standard technique, the sensitivity for malignant lesions was 96.1%; the sensitivity for benign lesions, 92.1%; and diagnostic accuracy, 94.4%. Thirty-seven patients (41.6%) had pneumothorax, with 16 (18.0%) requiring chest tube placement. When using the puncture site-down positioning technique, the sensitivity for malignant lesions was 95.4%; the sensitivity for benign lesions, 93.3%; and diagnostic accuracy, 94.6%. Nineteen patients (12.9%) had pneumothorax, with four (2.7%) requiring chest tube placement. Other complications were minimal. CT-guided transthoracic needle biopsy using the puncture site-down positioning technique is an effective and safe procedure with a high diagnostic accuracy and low complication rate. This new technique is especially useful in reducing the rate of pneumothorax.


Association of Serum Bile Acid and Unsaturated Fatty Acid Profiles with the Risk of Diabetic Retinopathy in Type 2 Diabetic Patients.
We aimed to identify the ability of serum bile acids (BAs) and unsaturated fatty acids (UFAs) profiles to predict the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients. We first used univariate and multivariate analysis to compare 15 serum BA and 11 UFA levels in healthy control (HC) group (n = 82), T2DM patients with DR (n = 58) and T2DM patients without DR (n = 60). Forty T2DM patients were considered for validation. Then, the receiver operating characteristic curve (ROC) and decision curve analysis were used to assess the diagnostic value and clinical benefit of serum biomarkers alone, clinical variables alone or in combination, and the area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to further assess whether the addition of biomarkers significantly improved the predictive ability of the model. Orthogonal partial least squares-discriminant analysis (OPLS-DA) of serum BAs and UFAs separated the three cohorts including HC, T2DM patients with or without DR. The difference in serum BA and UFA profiles of T2DM patients with or without DR was mainly manifested in the three metabolites of taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA) and arachidonic acid (AA). Together, they had an AUC of 0.785 (0.918 for validation cohort) for predicting DR in T2DM patients. After adjusting for numerous confounding factors, TLCA, TUDCA, and AA were independent predictors that differentiated T2DM with or without DR. The results of AUC, IDI, and NRI demonstrated that adding these three biomarkers to a model with clinical variables statistically increased their predictive value and were replicated in our independent validation cohort. These findings highlight the association of three metabolites, TLCA, TUDCA and AA, with DR and may indicate their potential value in the pathogenesis of DR.


A Grand Challenge. 3. Unbiased Phenotypic Function of Metabolites from Australia Plants Gloriosa superba and Alangium villosum against Parkinson's Disease.
As part of a continuing research program aiming to identify chemical probes to interrogate Parkinson's disease (PD), we have investigated the Australian plants Gloriosa superba and Alangium villosum. The chemical investigations of G. superba resulted in the isolation of four new alkaloids, β-lumicolchicosides A-C (1-3) and γ-lumicolchicoside A (4), together with four lumicolchicine derivatives (5-8) and six colchicine analogues (9-14) as known structures. The chemical investigations of A. villosum resulted in the isolation of four new benzoquinolizidine N-oxides, tubulosine Nβ5-oxide (15), isotubulosine Nα5-oxide (16), 9-demethyltubulosine Nβ5-oxide (17), and 9-demethylisotubulosine Nα5-oxide (18), together with five known benzoquinolizidine alkaloids (19-23). The chemical structures of the new compounds (1-4 and 15-18) were characterized unambiguously by extensive analysis of their NMR and MS data. Unbiased multidimensional profiling was used to investigate the phenotypic profiles of all of the metabolites. The results show that the lead probes have different effects on cellular organelles that are implicated in PD in patient-derived cells.


Quantum size effects in the polarizability of carbon fullerenes.
We investigate the size-dependent dielectric response of carbon fullerenes with up to 3840 atoms in the framework of the linear response theory. Our results suggest a significant polarizability enhancement due to quantum size effects with respect to classical or semiclassical calculations. The accuracy of our results, based on a parametrized Hamiltonian, is verified by ab initio time dependent density functional calculations for smaller fullerenes. Our findings underline the importance of quantum effects in the electronic response of nano- and mesoscopic systems.


Premenstrual syndrome. A double-blind cross-over study of treatment with dydrogesterone and placebo.
A double-blind, cross-over, placebo-controlled study of dydrogesterone (10 mg b.d.) in the treatment of premenstrual syndrome is described. Two groups of women were studied: secondarily referred hospital clinic patients, and self-referred patients. Only one-third of patients screened completed the study. All patients showed significant improvements in symptom scores during the course of the study, the only significant difference between placebo- and dydrogesterone-treated patients being an increase in frequency of breast tenderness and a decrease in pain with menstrual bleeding in the latter.


The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer.
Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.


Altered metabolomic-genomic signature: A potential noninvasive biomarker of epilepsy.
This study aimed to identify noninvasive biomarkers of human epilepsy that can reliably detect and localize epileptic brain regions. Having noninvasive biomarkers would greatly enhance patient diagnosis, patient monitoring, and novel therapy development. At the present time, only surgically invasive, direct brain recordings are capable of detecting these regions with precision, which severely limits the pace and scope of both clinical management and research progress in epilepsy. We compared high versus low or nonspiking regions in nine medically intractable epilepsy surgery patients by performing integrated metabolomic-genomic-histological analyses of electrically mapped human cortical regions using high-resolution magic angle spinning proton magnetic resonance spectroscopy, cDNA microarrays, and histological analysis. We found a highly consistent and predictive metabolite logistic regression model with reduced lactate and increased creatine plus phosphocreatine and choline, suggestive of a chronically altered metabolic state in epileptic brain regions. Linking gene expression, cellular, and histological differences to these key metabolites using a hierarchical clustering approach predicted altered metabolic vascular coupling in the affected regions. Consistently, these predictions were validated histologically, showing both neovascularization and newly discovered, millimeter-sized microlesions. Using a systems biology approach on electrically mapped human cortex provides new evidence for spatially segregated, metabolic derangements in both neurovascular and synaptic architecture in human epileptic brain regions that could be a noninvasively detectable biomarker of epilepsy. These findings both highlight the immense power of a systems biology approach and identify a potentially important role that magnetic resonance spectroscopy can play in the research and clinical management of epilepsy.


Brain monoaminergic activity in rainbow trout selected for high and low stress responsiveness.
This paper investigates whether two lines of rainbow trout displaying genetically determined variation in stress responsiveness and behavior also show differences in brain monoaminergic activity. In several brain regions, strains of rainbow trout selected for consistently high or low post-stress cortisol levels displayed differences in tissue concentrations of monoamines and/or monoamine metabolites, or in metabolite/monoamine ratios. High-responsive trout reacted to stress by an increase in the concentrations of both serotonin (brain stem), dopamine (brain stem), and norepinephrine (optic tectum, telencephalon), whereas low-responsive fish did not. Brain stem and optic tectum concentrations of monoamine metabolites were also elevated after stress in high responders, but not in low-responsive fish. The simultaneous increase in the concentration of monoamines and their metabolites suggests that both synthesis and metabolism of these transmitters were elevated after stress in high-responsive trout. A divergent pattern was seen in the hypothalamus, where low-responsive fish displayed elevated levels of 5-hydroxyindoleacetic acid (a serotonin metabolite) and 3-methoxy-4-hydroxyphenylglycol (a norepinephrine metabolite). In the telencephalon, both populations had elevated concentrations of these metabolites after stress. These results clearly suggest that selection for stress responsiveness in rainbow trout is also associated with changes in the function of brain monoaminergic systems. The possible functional significance of these observations is discussed with respect to the physiological and behavioral profile of these strains of fish. Literature is reviewed showing that several factors affecting brain monoaminergic activity might be altered by selection for stress responsiveness, or alternatively be under direct influence of circulating glucocorticoids.


Effect of ramipril therapy on cognitive functions in cases of mild to moderate essential hypertension.
Several studies have questioned the effect of hypertension on cognitive functions. Event related potentials (P300) have been used as a reliable and reproducible indicator of cognitive functions. In this non-randomized, open label study we investigated cognitive functions using event related potentials in newly diagnosed mild to moderate essential hypertensive patients and whether or not there was any effect of antihypertensive treatment with angiotensin converting enzyme inhibitor ramipril on the event related potentials. We selected twenty male patients of newly diagnosed mild to moderate essential hypertension by using ambulatory blood pressure monitoring who were previously untreated and compared their event related potentials with 10 normotensive controls. At the beginning of the study, the hypertensive group showed increased P300 and N2 wave latency as compared to the normotensive control subjects. After three months of Ramipril therapy at a dose of 5mg per day, there was a significant decrease in all the ambulatory blood pressure parameters and the mean P300 latency from the pretreatment values. But no significant change in the N2 latency was observed. Thus, treatment with Ramipril 5 mg daily for a period of three months can reverse some aspects of cognitive dysfunction associated with hypertension.


Immunization today--a review.
Immunization practices are frequently changing as our understanding of the basic concepts of host-parasite interactions grows and research in the area of new vaccines continues. The present review attempts to summarize current practices and the scientific data on which they are based. A complete historical review of the subject is beyond the scope of this report which is only intended to survey developments in the field over the past few years and up until October 1972.


Examining family planning and adverse pregnancy outcomes for women with active tuberculosis disease: a systematic review.
(1) Summarise and evaluate the current evidence of tuberculosis (TB)-associated pregnancy outcomes, (2) evaluate the state of the science of family planning during TB treatment and (3) provide recommendations to move forward to improve care and outcomes during TB disease. Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed, Embase, CINAHL, Cochrane, Web of Science and Scopus were searched from September 2009 to November 2021. Studies were included if they assessed pregnant women with active TB, drug-resistant TB (DR-TB) or TB/HIV coinfection and examined pregnancy, maternal, fetal/birth and TB or TB/HIV coinfection outcomes. Studies were also included if they examined family planning services among women initiating TB treatment. Two independent reviewers extracted data using PRISMA guidelines and conducted quality assessment using the Joanna-Briggs Institute Critical Appraisal Tools. The level of evidence was reported using the Johns Hopkins Evidence-Based Practice guidelines. 69 studies were included in this review. Case reports, case series, case controls, cohort studies, secondary data analyses and a service delivery improvement project conducted in 26 countries made up the totality of the evidence. Most studies reported pregnancy complications for mothers (anaemia, postpartum haemorrhage, deaths) and fetuses or newborns (low birth weight, premature birth, and spontaneous or induced abortions). Few studies discussed the value of offering family planning to prevent adverse pregnancy outcomes. One study examined the effect of a provider training on contraceptive use with reported increased contraceptive use. Integrating family planning services within a TB treatment programme is essential to reduce adverse TB-associated maternal-child outcomes. Despite well-established adverse pregnancy outcomes, little attention has been paid to family planning to prevent poor pregnancy outcomes for women with TB/DR-TB. Recommendations for clinicians, TB programmes and researchers are provided and reflect evidence presented in this review.


Genetic changes with prognostic value in histologically benign meningiomas.
Meningiomas add up to 25% of intracranial tumors. Although the majority is considered histologically benign, the prediction of their potential aggressiveness is still unclear. We studied the histopathology and aberrations of chromosomes 1p, 14, and 22 by FISH (fluorescence in situ hybridization) in histologically benign meningiomas of 70 patients for the purpose of defining the prognostic value of these alterations in tumoral progression and the risk of recurrence. According to the WHO histopathological criteria, the study set comprised 53 benign, 11 atypical, and 6 anaplastic meningiomas. In benign meningiomas, 25% of the cases displayed a normal karyotype, isolated monosomy 22 (36%), monosomy 22 + 1p deletion (14%), 1p deletion (10%), monosomy 22 + 14q deletion (5%), monosomy 22 + 1p deletion + 14q deletion (5%), or other alterations (5%). Grade II meningiomas presented losses in chromosome 14 in most of the cases (67%), and Grade III meningiomas showed alterations in chromosome 14 in all patients. We observed an overall relapse rate of 31%: recurrence was observed in 19% of Grade I meningiomas, 64% of Grade II, and 83% of Grade III. 9 out of 10 recurrent cases revealed abnormalities in chromosomes 1 and 14, which was a notably higher incidence compared to the series of tumors without relapse. Thus, benign meningiomas with cytogenetic alterations in chromosomes 1p and 14 may be more closely related to atypical meningiomas than benign meningiomas without these alterations, especially in terms of recurrence risk.


Setting health care priorities: Oregon's next steps.
Since the proposal was first broached in 1987, a storm of controversy has engulfed Oregon's plan to prioritize the health care services offered to its Medicaid recipients. After two years of debate, community consultation, and public opinion polls, the Oregon Health Services Commission was mandated in 1989 to study prioritization as part of a package of bills enacted as the Oregon Basic Health Services Act. In March 1990 the commission released a draft list of ranked health care services for public comment... As part of the ongoing debate, the Hastings Center and the Wesley Foundation sponsored a two-day meeting in January 1991 in Wichita, Kansas, to provide opportunity for thoughtful, in-depth, informal analysis of the OBHSA model for health care reform...a majority felt that OBHSA, in the framework of progress toward larger reform goals, is an experiment worth trying. Some felt that even if OBHSA doesn't attain its larger goals it should be tried since it will extend access and may lead to better health outcomes among the poor. But the general view was that OBHSA is a valuable experiment only to the extent that it leads to a statewide system of universal health insurance in Oregon without creating special burdens for the state's poor....


The effect of extracorporeal shock wave therapy in acute traumatic spinal cord injury on motor and sensory function within 6 months post-injury: a study protocol for a two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled clinical trial.
The pathological mechanism in acute spinal cord injury (SCI) is dual sequential: the primary mechanical lesion and the secondary injury due to a cascade of biochemical and pathological changes initiated by the primary lesion. Therapeutic approaches have focused on modulating the mechanisms of secondary injury. Despite extensive efforts in the treatment of SCI, there is yet no causal, curative treatment approach available. Extracorporeal shock wave therapy (ESWT) has been successfully implemented in clinical use. Biological responses to therapeutic shock waves include altered metabolic activity of various cell types due to direct and indirect mechanotransduction leading to improved migration, proliferation, chemotaxis, modulation of the inflammatory response, angiogenesis, and neovascularization, thus inducing rather a regeneration than repair. The aim of this clinical study is to investigate the effect of ESWT in humans within the first 48 h after an acute traumatic SCI, with the objective to intervene in the secondary injury phase in order to reduce the extent of neuronal loss. This two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled study has been initiated in July 2020, and a total of 82 patients with acute traumatic SCI will be recruited for the first stage in 15 participating hospitals as part of a two-armed three-stage adaptive trial design. The focused ESWT (energy flux density: 0.1-0.19 mJ/mm2, frequency: 2-5 Hz) is applied once at the level of the lesion, five segments above/below, and on the plantar surface of both feet within the first 48 h after trauma. The degree of improvement in motor and sensory function after 6 months post-injury is the primary endpoint of the study. Secondary endpoints include routine blood chemistry parameters, the degree of spasticity, the ability to walk, urological function, quality of life, and the independence in everyday life. The application of ESWT activates the nervous tissue regeneration involving a multitude of various biochemical and cellular events and leads to a decreased neuronal loss. ESWT might contribute to an improvement in the treatment of acute traumatic SCI in future clinical use. ClinicalTrials.gov NCT04474106.


Results from Polish Spondyloarthritis Initiative registry (PolSPI) - methodology and data from - the first year of observation.
Report on one-year results from the Polish Spondyloarthritis Initiative registry (PolSPI), containing the cross-sectional analysis of clinical and imaging data as well as database methodology. The PolSPI registry includes patients with axial (axSpA) and peripheral (perSpA) spondyloarthritis according to ASAS classification criteria, and/or patients with ankylosing spondylitis according to modified New York criteria, psoriatic arthritis according to CASPAR criteria, arthropathy in inflammatory bowel disease, reactive arthritis, juvenile spondyloarthritis or undifferentiated spondyloarthritis. Epidemiologic data and history of signs, symptoms and treatment of spondyloarthritis are collected and assessment of disease activity is performed. Radiographic images of sacroiliac joint, cervical and lumbar spine, and results of bone densitometry are collected. Every 6 months blood samples for inflammatory markers, and for long-term storage are taken. During a one-year period from September 2015 to August 2016, 63 patients were registered on an electronic database; 44 (69.8%) of patients were classified as axial spondyloarthritis (axSpA) and 19 (30.2%) as peripheral spondyloarthritis (perSpA) according to ASAS criteria. Statistically significant differences between axSpA and perSpA were discovered in the percentage of HLA-B27 antigen occurrence (92.6% and 50%, respectively), BASDAI (2.8% and 4.1%, respectively), DAS 28 (2.66% and 4.03%, respectively), percentage of peripheral arthritis (20% and 88.8%, respectively), enthesitis (26.7% and 70.6%, respectively), dactylitis (6.7% and 88.9%, respectively), as well as extra-articular symptoms: acute anterior uveitis (26.7% and 5.6%, respectively) and psoriasis (6.9% and 55.6%, respectively). Patients with axSpA had significantly higher mean grade of sacroiliac involvement according to New York criteria, higher mSASSS score, and lower T-score in femoral neck in bone densitometry. At the early stage of the disease patients with axSpA compared to those with perSpA, have more advanced structural damage of sacroiliac joints and spine, and lower bone mineral density in the femoral neck. In the upcoming years the PolSPI registry will prospectively follow-up patients with SpA, recording response to treatment and carrying out research on interaction of inflammation and bone remodelling.


Comparison of gastric juice soluble triggering receptor expressed on myeloid cells and C-reactive protein for detection of Helicobacter pylori infection.
Triggering receptor expressed on myeloid cells (TREM-1) is a receptor on phagocytes that is triggered by infectious agents. The soluble form of it (sTREM-1) can be elevated in gastric juice by Helicobacter pylori (H. pylori) infection of gastric mucosa. The aim of this study was to compare the diagnostic values of sTREM-1 and C-reactive protein (CRP) for detection of H. pylori infection in gastric mucosa. In this diagnostic accuracy study on cases who underwent endoscopy from March 2015 to July 2016 in Shahid Beheshti Hospital, Kashan, Iran, gastric juice sTREM-1 and CRP concentrations were measured by enzyme-linked immunosorbent assays (ELISA) and their diagnostic values were compared to detect H. pylori infection. Gold standard test was histopathology. Data were entered into SPSS software version 16. Statistical analysis was made by Kolmogorov-Smirnov, Chi-square, Independent-samples t-test, Kruskal-Wallis, Mann-Whitney U, Pearson product-moment correlation, Receiver operating characteristic curve (ROC), Brier score, Nagelkerke R square and scaled reliability test. Of a total of 160 cases, 81 (50.6%) were H. pylori-positive based on pathology. The level of sTREM-1 in H. pylori-positive patients was significantly higher than H. pylori-negative patients (p=0.000), but no significant difference between CRP concentrations was shown between groups (p=0.7). Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and accuracy of sTREM-1 were 82%, 75%, 3.3, 0.25, 78% and for CRP were 62%, 40%, 1.02, 0.98, 51% respectively for diagnosis of H. pylori infection. True positive and negative rates were 66 (81.5%) and 59 (74.7%) for sTREM-1 and 50 (61.7%) and 31 (39.2%) for CRP. The levels of sTREM-1 and CRP were not significantly different between endoscopic finding groups (p=0.97, p=0.2 respectively). Despite CRP, sTREM-1 was a relatively acceptable indicator of H. pylori infection of gastric mucosa.


The ratio "circulating red cell volume/lean body mass" in normal and hypophysectomized rats on paired feeding.
The ratio "circulating red cell volume/lean body mass" was calculated in normal and hypophysectomized male rats put on paired feeding for 90 days after hypophysectomy, and in control rats both at the beginning and the end of this experimental period. Control rats at the onset of the experiment, hypophysectomized rats, and rats on the sub-maintenance level of food consumption did not show a significant difference in their red cell volumes/lean body mass ratios. These values were significantly lower than those of sham hypophysectomized rats allowed to eat ad libitum. These results suggest that the reduction in the feed intake that follows pituitary ablation may play an important role in the genesis of the post-hypophysectomy anemia.


Comparison of weekly and daily incremental protocols of narrowband ultraviolet B phototherapy for psoriasis.
Different protocols have been used for narrowband ultraviolet B (UVB) therapy, commonly used in the treatment of psoriasis; however, more effective and reliable protocols are still required. The aim of this study was to compare the weekly and daily dose increment protocols of narrowband UVB phototherapy in psoriasis patients. Thirty patients with plaque psoriasis underwent narrowband UVB treatment three times a week and 15 patients selected consecutively among these patients underwent a weekly (once in three treatments) dose increment whereas the remaining 15 patients underwent a daily dose increment. Patients were monitored for 10 weeks and evaluated by the Psoriasis Area Severity Index (PASI). When the two groups were evaluated according to median PASI scores prior to the treatment and during 10 weeks of treatment, there was no statistically significant difference between the groups (P > 0.05). During the treatment lasting for 10 weeks, four patients in the group with a weekly dose increment and three patients in the group with a daily dose increment recovered and no statistically significant difference was detected between the groups (P > 0.05). The groups were also evaluated according to the median cumulative dose. The median cumulative dose was higher in the group with a daily dose increment and the difference between the groups was statistically significant (P = 0.002). The application of daily dose increments was no better than that of weekly dose increments in narrowband UVB treatment for psoriasis. Therefore, although our results may need to be supported by large-series studies, we conclude that application of weekly dose increments with a lower cumulative dose having the same efficacy is preferred in narrowband UVB treatment of psoriasis.


A comparison of lipid and lipoprotein measurements in the fasting and nonfasting states in patients with type 2 diabetes.
Patients with diabetes often do not reach recommended lipid targets. This may be in part due to the difficulty of obtaining fasting measurements. To compare fasting and nonfasting low density lipoprotein cholesterol (LDLc), non-high density lipoprotein cholesterol (non-HDLc), and low density lipoprotein particle number (LDLP) patients with type 2 diabetes (T2DM) and to determine the effect on assessing treatment success. Standard lipids and NMR lipoproteins were analyzed at baseline and following a standardized meal in patients with T2DM. Primary outcomes were agreement between fasting and nonfasting LDLc, non-HDLc, and LDLP and the agreement between these measures for determining fasting LDLc treatment success. Direct LDL cholesterol (DLDL) was a secondary outcome. Of 31 patients, only 56% of LDLc measurements were equivalent in the fasting and nonfasting states, compared to 97% of DLDLc (p < 0.0001), 94% of non-HDLc (p < 0.001) and 77% of LDLP (p < 0.01) measurements. Assessment of nonfasting lipid values would have resulted in misclassification by treatment target in 15% of LDLc, 3.2% of DLDLc assessments (p < 0.05 vs. LDLc), and 0% of non-HDLc and LDLP assessments (p < 0.01 vs. LDLc). Nonfasting LDLc, non-HDLc, LDLP, and DLDLc correctly identified fasting LDLc classification in 23/27 (85%), 26/30 (87%, p = NS vs. nonfasting LDLc), 16/30 (53%, p < 0.001 vs. nonfasting LDLc), and 24/30 (80%, p = NS vs. nonfasting LDLc), respectively. If confirmed in larger studies, nonfasting non-HDLc may be a suitable proxy for fasting LDLc in patients with T2DM.


Multifractal Conductance Fluctuations of Helical Edge States.
Two-dimensional topological insulators are characterized by the bulk gap and one-dimensional helical states running along the edges. The theory predicts the topological protection of the helical transport from coherent backscattering. However, the unexpected deviations of the conductance from the quantized value and localization of the helical modes are generally observed in long samples. Moreover, at millikelvin temperatures significant mesoscopic fluctuations are developed as a function of the electron energy. Here we report the results of an experimental study of the transport in a HgTe quantum well with an inverted energy spectrum that reveal a multifractality of the conductance fluctuations in the helical edge state dominated transport regime. We attribute observed multifractality to mesoscopic fluctuations of the electron wave function or local density of states at the spin quantum Hall transition. We have shown that the mesoscopic two-dimensional topological insulator provides a highly tunable experimental system in which to explore the physics of the Anderson transition between topological states.


Self-Assembled Monolayers for Dental Implants.
Implant-based therapy is a mature approach to recover the health conditions of patients affected by edentulism. Thousands of dental implants are placed each year since their introduction in the 80s. However, implantology faces challenges that require more research strategies such as new support therapies for a world population with a continuous increase of life expectancy, to control periodontal status and new bioactive surfaces for implants. The present review is focused on self-assembled monolayers (SAMs) for dental implant materials as a nanoscale-processing approach to modify titanium surfaces. SAMs represent an easy, accurate, and precise approach to modify surface properties. These are stable, well-defined, and well-organized organic structures that allow to control the chemical properties of the interface at the molecular scale. The ability to control the composition and properties of SAMs precisely through synthesis (i.e., the synthetic chemistry of organic compounds with a wide range of functional groups is well established and in general very simple, being commercially available), combined with the simple methods to pattern their functional groups on complex geometry appliances, makes them a good system for fundamental studies regarding the interaction between surfaces, proteins, and cells, as well as to engineering surfaces in order to develop new biomaterials.


Trainee Surgeons Affect Operative Time but not Outcome in Minimally Invasive Total Hip Arthroplasty.
Training of young surgeons in total hip arthroplasty (THA) is crucial, but might affect operative time and outcome especially in minimally invasive (MIS) THA. We asked whether the learning curve of orthopaedic residents trained on MIS THA has an impact on (1) operative time (2) complication rates and (3) early postoperative outcome. In a retrospective analysis of over 1000 MIS THAs from our institutional joint registry, operative time, complication rates, patient reported outcome measures (Western Ontario and McMaster Universities Arthritis Index [WOMAC] and Euro-Qol 5D-5L [EQ-5D]) within the first year and responder rates for positive outcome as defined by the Outcome Measures in Rheumatology and Osteoarthritis Research Society International consensus responder (OMERACT-OARSI) criteria were compared between trainee and senior surgeons. Mean operative time was nine minutes longer for trainees compared to senior surgeons (78.1 ± 25.4 min versus 69.3 ± 23.8 min, p < 0.001). Dislocation (p = 0.21), intraoperative fracture (p = 0.84) and infection rates (p = 0.58) were comparably low in both groups. Both trainee and senior THAs showed excellent improvement of EQ-5D (0.34 ± 0.26 versus 0.32 ± 0.23, p = 0.40) and WOMAC (45.9 ± 22.1 versus 44.9 ± 20.0, p = 0.51) within the first year after surgery without clinical relevant differences. Similarly, responder rates for positive outcome were comparable between trainees with 92.9% and senior surgeons with 95.2% (p = 0.17). MIS THA seems to be a safe procedure during the learning curve of young orthopaedic specialists, but requires higher operative time.


The development of vertebral bone marrow of human fetuses.
The development of the bone marrow of the thoracic vertebrae in seven human fetuses ranging from 95 to 150 mm in crown-rump length (CRL) was studied using light and electron microscopy. In the 95-mm CRL, hypertrophy of the chondrocytes occurred in the central region of the vertebrae, and blood vessels penetrated there from dorsal and ventral sides of the vertebral body. The primary marrow was represented by liberated cartilage lacunnae, occupied by the thin-walled blood vessels and a few mesenchymal cells and mononuclear cells containing granules or vacuoles (GMC). In the 99-mm CRL, chondroclasts were active in removing the cartilage near the central region of the vertebrae. Consequently, a large cavity was formed and occupied by a dilated sinus. GMC were numerous. Osteoblasts and osteocytes were increased in number. Reticular cells with long processes containing large amounts of glycogen began to appear in the extravascular space and formed the loosely arranged cellular meshwork of the hematopoietic compartment. Bundles of collagen fibrils were scattered in the meshwork. Hematopoietic cells were recognizable only in the 105-mm-CRL fetus and increased in number in the 120-mm-CRL fetus. The sinus endothelium was very thin and continuous without apertures except where blood cells crossed the wall. The developing blood cells lying against the outside of the sinus endothelium indented it. At points, collagen fibrils attached to the outside of endothelial cells and appeared to function as the anchoring filaments of lymphatics. The physiologic implications of the association of stromal cells, vascular sinuses, and hematopoietic cells are discussed in relationship to the microhematopoietic environment of the bone marrow.


Taiwan ozone trend in response to reduced domestic precursors and perennial transboundary influence.
Two decades of nitrogen oxides (NOx) and volatile organic compounds (VOCs) in ambient concentrations have been continuously reduced by nearly 60% since 1994. However, the annual mean ozone (O3) concentrations in Taiwan had leveled off for more than a decade. Furthermore, the significant cuts in precursors did lead to reduction in episodic days (O3≥ 100 ppbv) over time, implying the weakened photochemical production of O3. Simultaneously, the number of low O3 days (O3 < 20 ppbv) also decreased due to weakened NO titration. Nevertheless, the reduction of both high and low O3 days resulted in an increase in the number of medium O3 days (O3 from 60-80 ppbv). While the nighttime mean O3 continued to increase, the daytime mean O3 leveled off and coincided with the marine background concentration of approximately 40 ppbv, revealing a gradual decrease in the daytime-nighttime mean O3 difference. In addition to multiple chemical reasons, transboundary O3 from Asian continental outflow is thought to be another major contributor to the prolonged leveling of domestic O3. To quantitatively illustrate the role of the transboundary effect, model simulations were conducted in two ways: one assessed the time percentage of a year affected by the transboundary influence; and the other involved decoupling the transboundary O3 from the domestically produced O3 to quantify the amount of domestic O3 that can be mitigated by prescribing scenarios; namely, the so-called sensitivity test. The sensitivity test suggests that although controlling domestic emissions is still vital to contain O3 under weak transboundary conditions, the overall O3 averages and the long-term trend at the island scale are closely associated with the transboundary influence. The gradual increased medium O3 concentrations to approximate the marine background level could imply that future O3 concentration on the island will be more influenced more by the transboundary conditions and less relevant to the domestic containment measures.


Glutamate receptor RNA editing: a molecular analysis of GluR2, GluR5 and GluR6 in human brain tissues and in NT2 cells following in vitro neural differentiation.
The properties of some glutamate receptors are modified by RNA editing. This post-transcriptional mechanism involves the enzymatic deamination of specific adenosines in the pre-mRNA of the glutamate receptors, performed by specific RNA adenosine deaminases (ADARs). This event gives rise to the substitution of a gene-encoded amino acid with a different one that modifies the physiological properties of the ion channel. Here we report an analysis of the editing levels of AMPA GluR2, and kainate GluR5 and GluR6 in a human teratocarcinoma cell line (NT2) during in vitro neural differentiation, in conjunction with an analysis of the expression levels of GluR and ADAR genes. The editing levels were analysed using a specific standardised assay based on sequence analysis. This assay can be performed on all editing sites with a high level of sensitivity and reproducibility. Whereas GluR gene expression increased during NT2 neural differentiation, the expression of ADAR genes may be detected at comparable levels even in undifferentiated NT2 cells, remaining relatively stable during the differentiation process. Furthermore, most of the glutamate receptor editing sites increased their editing levels during NT2 neural differentiation, suggesting that the level of ADAR mRNAs is not closely related to the variable editing levels detected in the GluRs analysed. In human brain tissues, the editing levels appeared finely modulated in the different areas, indicating the possible formation of ion channels with different functional properties, thus generating a complex tissue-specific regulation of receptors and modulation of excitatory stimuli.


Vascular contraction: effect of age and extracellular calcium.
Contractile responses to norepinephrine, serotonin and potassium chloride were determined in vitro for aortas from rats 1, 2, 3 and 12 months of age. Responses were measured under conditions of optimum length (3 cm) and resting tension (1 g). Aortic response to a maximum concentration of norepinephrine was greatest for vessels from 3-month-old rats. For all three agonists, aortas from 12-month-old rats contracted less than aortas from 2-month-old rats. The role of calcium in aortic contraction also varied with age. For rats 1-2 months of age, serotonin and potassium chloride-induced contractions were highly dependent on extracellular calcium, while norepinephrine-induced contraction showed only a slight dependence on extracellular calcium. In 12-month-old rats, all agonists were dependent on extracellular calcium for contraction. For serotonin and norepinephrine, the ability of muscle to contract in calcium-free media was decreased with age. Although the mechanism for such an altered dependence of aortic contraction on calcium has not been established, it is proposed that the utilization of extracellular calcium for contraction is not only agonist- but also age-dependent.


Characterizing Comorbid Cerebrovascular Insults Among Patients With TBI at a TBI Model Systems Rehabilitation Center.
Determine incidence and predictors of comorbid cerebrovascular injuries in patients with moderate to severe traumatic brain injury (TBI) and whether it influences rehabilitation outcomes. Inpatient Rehabilitation Facility (IRF) brain injury unit participating in NIDILRR TBI Model Systems (TBIMS). A total of 663 patients with moderate to severe TBI. Observational study with prospective and retrospective data collection. New traumatic cerebral artery injury (TCAI) lesions of head/neck and new cerebral infarcts (CIs) abstracted from neuroimaging reports and clinical notes. The incidence of comorbid CI was 8%, among whom 19% also had TCAI identified. The incidence of TCAI increased over time from 2% before 2008 to 10% after, probably from greater screening. Both CI and TCAI were associated with longer acute care stay. Cerebral infarct was also associated with longer posttraumatic amnesia and lower rate of functional gains. Using in-depth abstraction of imaging findings, the incidence of traumatic head/neck artery injuries, and CIs in patients with moderate to severe TBI were both higher than a recent TBIMS-wide study utilizing ICD coding. Cerebral infarct was associated with longer posttraumatic amnesia duration and slower functional gains. Further research is recommended on the outcome implications of concomitant cerebrovascular injury in patients with TBI.


Development of a Dinitrosyl Iron Complex Molecular Catalyst into a Hydrogen Evolution Cathode.
Despite extensive efforts, the electrocatalytic reduction of water using homogeneous/heterogeneous Fe, Co, Ni, Cu, W, and Mo complexes remains challenging because of issues involving the development of efficient, recyclable, stable, and aqueous-compatible catalysts. In this study, evolution of the de novo designed dinitrosyl iron complex DNIC-PMDTA from a molecular catalyst into a solid-state hydrogen evolution cathode, considering all the parameters to fulfill the electronic and structural requirements of each step of the catalytic cycle, is demonstrated. DNIC-PMDTA reveals electrocatalytic reduction of water at neutral and basic media, whereas its deposit on electrode preserves exceptional longevity, 139 h. This discovery will initiate a systematic study on the assembly of [Fe(NO)2] motif into current collector for mass production of H2, whereas the efficiency remains tailored by its molecular precursor [(L)Fe(NO)2].


Precision Targeting of Endogenous Epidermal Growth Factor Receptor (EGFR) by Structurally Aligned Dual-Modifier Labeling.
Covalent modification of endogenous proteins by chemical probes is used for proteome-wide profiling of cellular protein function and drug discovery. However, probe selectivity in the complex cellular environment is a challenge, and new probes with better target selectivity are continuously needed. On the basis of the success of monocovalent activity-based and reactivity-based probes, an approach of structurally aligned dual-modifier labeling (SADL) was investigated here on its potential in improving target precision. Two reactive groups, based on the acrylamide and NHS ester chemistry, were linked with structural alignment to be under the same anilinoquinazoline ligand-directive for targeting the epidermal growth factor receptor (EGFR) protein kinase as the model system for proteome-wide profiling. The SADL approach was compared with its monocovalent precursors in a label-free MaxLFQ workflow using MDA-MB-468 triple negative breast cancer cells. The dual-modifier probe consistently showed labeling of EGFR with improved precision over both monocovalent precursors under various controls. The workflow also labeled endogenous USP34 and PKMYT1 with high selectivity. Precision labeling with two covalent modifiers under a common ligand directive may broaden protein identification opportunities in the native environment to complement genetic and antibody-based approaches for elucidating biological or disease mechanisms, as well as accelerating drug target discovery.


Exenatide can inhibit calcification of human VSMCs through the NF-kappaB/RANKL signaling pathway.
Arterial calcification is an important pathological change of diabetic vascular complication. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important cytopathologic role in arterial calcification. The glucagon-like peptide-1 receptor agonists (GLP-1RA), a novel type of antidiabetic drugs, exert cardioprotective effects through the GLP-1 receptor (GLP-1R). However, the question of whether or not GLP-1RA regulates osteoblastic differentiation and calcification of VSMCs has not been answered, and the associated molecular mechanisms have not been examined. Calcifying VSMCs (CVSMCs) were isolated from cultured human arterial smooth muscle cells through limiting dilution and cloning. The extent of matrix mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot. Gene expression of receptor activator of nuclear factor-κB ligand (RANKL) was silenced by small interference RNA (siRNA). Exenatide, an agonist of GLP-1 receptor, attenuated β-glycerol phosphate (β-GP) induced osteoblastic differentiation and calcification of human CVSMCs in a dose- and time-dependent manner. RANKL siRNA also inhibited osteoblastic differentiation and calcification. Exenatide decreased the expression of RANKL in a dose-dependent manner. 1,25 vitD3 (an activator of RANKL) upregulated, whereas BAY11-7082 (an inhibitor of NF-κB) downregulated RANKL, alkaline phosphatase (ALP), osteocalcin (OC), and core binding factor α1 (Runx2) protein levels and reduced mineralization in human CVSMCs. Exenatide decreased p-NF-κB and increased p-AMPKα levels in human CVSMCs 48 h after treatment. Significant decrease in p-NF-κB (p-Ser(276), p-Ser(536)) level was observed in cells treated with exenatide or exenatide + BAY11-7082. GLP-1RA exenatide can inhibit human VSMCs calcification through NF-κB/RANKL signaling.


Vitamin E and retrolental fibroplasia: ultrastructural mechanism of clinical efficacy.
Administration of control, oral or combined intramuscular and oral vitamin E to 418 high risk, preterm infants (1500 g or less birth weight; 32 weeks or less gestational age; 305 surviving more than 10 weeks) led to raised peak plasma levels of the vitamin of between 0.6 and 3.3 mg% in three consecutive clinical trials. This early, non-toxic, prophylactic supplementation suppressed the development of severe retrolental fibroplasia when the antioxidant was given continuously from the first day of life until retinal quiescence. Studies of 63 pairs of eyes by transmission electron microscopy revealed that spindle cells (the embryonic precursors of inner retinal capillaries) were the primary target of the vitamin E-induced suppression of severe retrolental fibroplasia. Extensive increases in the gap junctions between adjacent spindle cells in unsupplemented infants, or in supplemented infants of 27 weeks gestational age or less, triggered both neovascularization from the most nascent capillaries at the rearguard-vanguard retinal interface, and dilatation and tortuosity in the rearguard (posterior) retinal vessels. Continuous vitamin E supplementation permanently preserved the embryonic state of the spindle cells in infants of 28 weeks gestational age or more, and transiently retarded gap junction increases in infants of 27 weeks gestational age or less.


Ocular Surface Squamous Neoplasia Associated with Atopic Keratoconjunctivitis.
To describe 2 cases of invasive squamous cell carcinoma that originated in the setting of severe atopic keratoconjunctivitis (AKC). Case one involved a 73-year-old male with atopic eczema and severe AKC who developed a limbal lesion suspicious for ocular surface squamous neoplasia (OSSN). Slit-lamp examination was significant for a new sessile lesion in the temporal limbal region of the left eye. The lesion was treated with excisional biopsy and cryotherapy. Topical therapy with mitomycin C, topical interferon alpha 2b, and topical 5-fluorouracil provided only partial control. Exenteration was eventually needed. Case two involved a 53-year-old male with history of severe AKC and eczema. Computed tomography imaging showed an infiltrative mass of the right orbit. Incisional biopsies confirmed conjunctival squamous cell carcinoma of both sides (invasive in the right eye, in situ in the left eye). Exenteration was needed for control of invasive carcinoma in the right eye. Squamous cell carcinoma was treated without success in spite of surgical excision and aggressive treatment with multiple topical agents and multiple applications of cryotherapy. Orbital exenteration was needed in both cases. Chronic inflammation associated with AKC may be a risk factor for the development of bilateral, diffuse, invasive, and recurrent OSSN that may require exenteration.


Increased prescription dose for large vessel intravascular brachytherapy.
Most randomized studies testing the effectiveness of IVBT were limited to vessels less than 4 mm diameter. In fact, it is now common to treat vessels larger than 4 mm. Accordingly, the authors instituted a prescription dose increase to 34 Gy at 2 mm from source center for vessels greater than 4.0 mm. The increase in prescription dose to 34 Gy at 2 mm from center is substantial, being 50% higher than the conventional maximum of 23 Gy. To take a close look at group of patients treated to 34 Gy, and for whom follow-up angiograms are available. Ten patients treated for ISR with a prescription dose of 34 Gy and for whom follow-up angiograms were available were studied. Beta-radiation brachytherapy was performed with a Novoste Beta-Cath System using a strontium-90 (beta) source (Best Vascular, Springfield, VA). Source lengths of 40 or 60 mm were used. A dose of 34 Gy was prescribed at 2 mm from the source center. Patients were re-catheterized from 2 to 21 months (median: 16 months) following IVBT, all for symptoms suggested of restenosis. All patients had some degree of ISR of the target vessel, but no IVBT-treated vascular segment showed angiographic signs of degeneration, dissection or aneurysm. The authors' clinical impression, along with detailed review of the 10 cases, suggest that using a 34 Gy prescription dose at 2 mm from source center does not result in increased toxicity.


Endogenous apolipoprotein E suppresses LPS-stimulated microglial nitric oxide production.
The human apolipoprotein (apo) E4 isoform is associated with an increased risk for Alzheimer's disease (AD) and poor prognosis after acute CNS injury. Addition of human apoE inhibits murine microglial activation in culture, suggesting that microglia might be an important physiological target of apoE. In the present study, we examined the role of endogenous murine apoE in modulating microglial nitric oxide (NO) production following lipopolysaccharide (LPS) stimulation. Brain cultures from apoE-deficient mouse pups showed enhanced NO production relative to cultures from wild-type mice and from transgenic mice expressing the human apoE3 isoform, demonstrating that endogenous apoE produced by glial cultures is capable of inhibiting microglial function. ApoE produced within the brain may suppress microglial reactivity and thus alter the CNS response to acute and chronic injury.


Tolerance of aquifer stoneflies to repeated hypoxia exposure and oxygen dynamics in an alluvial aquifer.
Aquatic insects cope with hypoxia and anoxia using a variety of behavioral and physiological responses. Most stoneflies (Plecoptera) occur in highly oxygenated surface waters, but some species live underground in alluvial aquifers containing heterogeneous oxygen concentrations. Aquifer stoneflies appear to be supported by methane-derived food resources, which they may exploit using anoxia-resistant behaviors. We documented dissolved oxygen dynamics and collected stoneflies over 5 years in floodplain wells of the Flathead River, Montana. Hypoxia regularly occurred in two wells, and nymphs of Paraperla frontalis were collected during hypoxic periods. We measured mass-specific metabolic rates (MSMRs) at different oxygen concentrations (12, 8, 6, 4, 2, 0.5 mg l-1, and during recovery) for 111 stonefly nymphs to determine whether aquifer and benthic taxa differed in hypoxia tolerance. Metabolic rates of aquifer taxa were similar across oxygen concentrations spanning 2 to 12 mg l-1 (P>0.437), but the MSMRs of benthic taxa dropped significantly with declining oxygen (P<0.0001; 2.9-times lower at 2 vs. 12 mg l-1). Aquifer taxa tolerated short-term repeated exposure to extreme hypoxia surprisingly well (100% survival), but repeated longer-term (>12 h) exposures resulted in lower survival (38-91%) and lower MSMRs during recovery. Our work suggests that aquifer stoneflies have evolved a remarkable set of behavioral and physiological adaptations that allow them to exploit the unique food resources available in hypoxic zones. These adaptations help to explain how large-bodied consumers might thrive in the underground aquifers of diverse and productive river floodplains.


Bronchodilators: new drugs and controversies.
After complete abstinence, regular use of short-acting beta 2-agonists results in an increase in early and late asthmatic (allergen) response, exercise-induced bronchoconstriction, and nonspecific airways responsiveness (methacholine). Regular use of long-acting beta 2-agonists also results in increased nonspecific airways responsiveness (methacholine) with or without concomitant inhaled corticosteroids and attenuates the response to escalating doses of inhaled short-acting beta 2-agonists such as might be used in an acute exacerbation. In spite of these findings, symptom control and bronchodilation are improved more with the addition of salmeterol than with a doubling of inhaled corticosteroid dose. Selective cyclic nucleotide phosphodiesterase inhibitors show promise in expanding the bronchodilator and anti-inflammatory effects of theophylline.


Metastatic variants of the B16 melanoma: metastasis is related to environmental conditions. Genetic and metabolic effects.
Using variant B16 metastatic melanomas, attempts were made to explore the effects of both genetic and metabolic environmental factors in vivo as well as in vitro, on specific steps in the metastatic process. Metastases of the progenitor tumour in black C57BL/6J mice arose from a stable, heritable, non-random, pre-existing subpopulation of metastatic cells. In vitro, the environment influenced both pigmentary and metastatic phenotypes of variant B16 metastatic melanomas. The possibility that cells from different strains may express a phenotype following reinoculation into syngeneic mice was also explored. The experimental results suggested that new, enhanced, heritable, metastasis-related characteristics can develop as a result of genetic changes in yellow Ay/a and C57BL/6J mice that are accompanied by pigmentary changes. Such genetic changes can determine unstable non-random and random epigenetic metastatic effects with enhancement in vivo or disappearance in vitro of spontaneous metastatic ability and of the number of metastases, as monitored by serial transfers of tumour cells in vivo.


Extremity injuries sustained by the UK military in the Iraq and Afghanistan conflicts: 2003-2014.
Extremity injuries predominate in warfare, however their nature, and overall burden to the individual and the health service is yet to be characterised for the UK military in the recent conflicts of Iraq and Afghanistan. We reviewed the all extremity injuries in survivors from the Joint Theatre Trauma Registry (JTTR) between 2003 and 2014. All cases recorded in the JTTR between the invasion of Iraq on the 19th March 2003 and cessation of combat operations in Afghanistan on the 27th October 2014, were examined. Casualties who were killed in action or died from their wounds were excluded. All extremity injury codes were included, capturing patients with soft tissue injuries but no fracture or amputation. Of 2348 UK combatants surviving injury in Iraq and Afghanistan, 1813 (77%) had extremity injuries; of these 205 (11%) had at least one amputation at the wrist/ankle or more proximal. Trans-tibial was the most common level of limb loss. Eighty five casualties lost 2 limbs, 83 of these (98%) lost both lower limbs and 17 lost 3 limbs. Aside from amputations, there were 1530 fractures, 501 (33%) involving the upper limb and 1029 (67%) in the lower limb and pelvis. The tibia was the most frequently fractured bone. Of the lower limb fractures, 597 (58%) were open compared with 344 (69%) in the upper limb. Total Length of Stay (LOS) following extremity injury was 24,486days or 69 years and 1 month; there were a total 2817 surgical episodes performed on extremities. Median length of stay Length of Stay (LOS) for major amputations (i.e. those at the wrist/ankle or more proximal) was 51days (IQR 30-65) with a median of 7 surgical procedures on their limbs (IQR 5-9). In casualties with fractures but no amputation, median LOS was 13days (IQR 6-25) with a median of 2 surgical procedures (IQR 1-4). Utilising a dedicated injury database, this study illustrates for the first time in the United Kingdom military population, that the extremities are involved in the vast majority of combat injuries and the large surgical workload required for their treatment.


Separation of PEGylated Gold Nanoparticles by Micellar Enhanced Electrospun Fiber Based Ultrathin Layer Chromatography.
Gold nanoparticles (AuNPs) are of great interest in many fields, especially in biomedical applications. Thiol terminated polyethylene glycol (PEG) is the most widely used polymer to increase the biocompatibility of nanoparticle therapeutics. Herein, a rapid method for separation and characterization of PEGylated AuNPs on an ultrathin layer chromatographic (UTLC) plate using electrospun polyacrylonitrile (PAN) nanofibers as the stationary phase is described. AuNPs with sizes ranging from 10 to 80 and 30 nm AuNPs coated with various molecular weight of PEG (2, 5, 10, and 20 kDa) were all successfully separated by UTLC using optimized conditions. The fabrication of electrospun UTLC is simple, fast, and inexpensive. The UTLC, with much thinner sorbent layer (10× thinner than traditional TLC) and small fiber size (∼300 nm), requires minimal mobile phase solvent and provides faster separation and higher resolution compared to other separation methods for AuNPs. AuNPs with different sizes and different PEG molecular weights were well separated within 5 min with lowest plate height <2 μm and resolution value >1.5. As an example of this method, the size transformation of AuNPs in serum protein was determined quantitatively.


The experimental production of increased eosinophils in rat late-phase reactions.
The effects of peripheral eosinophilia on the intensity, kinetics and cellular characteristics of rat cutaneous late-phase reactions (LPR) have been investigated. Two distinct methods of inducing peripheral eosinophilia did not alter either the intensity or the kinetics of LPR produced by the intradermal injection of anti-IgE, Compound 48/80, or isolated mast cell granules. Hypereosinophilic animals exhibited increased numbers of tissue eosinophils in LPR tissue sites which correlated with the elevations in their respective peripheral eosinophil counts; however, the absolute number of eosinophils present, although significant, was not impressive (less than 10% of total). Our data suggest that, although rat LPR can be modulated to involve increased tissue eosinophils by increasing the numbers of peripheral blood eosinophils, no effects of these procedures on altering either the intensity or the kinetics of these reactions can be appreciated.


Effects of permanent dipole moments in transient four-wave mixing experiments.
A two-pulse degenerate four-wave mixing experiment is analyzed in the case where the medium under investigation can be modeled by two-level systems having unequal permanent dipole moments. By modeling the light pulses by double exponentials [exp(-Gamma/t/)], we give an analytical expression of the third-order nonlinear polarization of the medium. We apply this result to simulate the measured signal in such experiment. We show that in the case of a two-photon transition, a signal can be detected if the pump pulse interacts with the medium before the probe pulse contrary to what is observed for excitations in the resonance region. An attempt to explain this behavior is made and the detected signal is analyzed in terms of pure coherent processes. This effect appears as a signature of the presence of permanent dipole moments. To test this property on a more realistic system, we then have considered a one-dimensional frequency-selected infrared degenerate four-wave mixing experiment on a molecular anharmonic vibrational mode modeled by a Morse potential and coupled to a dissipative bath of harmonic oscillators. We show that the two-photon transitions allowed by the presence of permanent dipole moments enable to analyze the multilevel system dynamics as if they were the one of a two-level system. Our results can also be extended to the case of inhomogeneous broadening and are of interest to study the infrared photon-echo response of anharmonic vibrational modes.


Medicine and hagiography in Italy c. 800-c. 1000.
A vast range of sources, from chronicles, hagiography and the liturgy to medical manuscripts and charters, is at our disposal for the study of health and healing in Italy between the ninth and eleventh centuries. What is needed in order to exploit this material is a methodology for the careful examination of sources in their regional, social and political context. I focus on what hagiography can contribute to the study of medicine and disease, discussing in detail two ninth-century episcopal hagiographies, the Milanese second Vita Ambrosii, and the Vita Barbati from Benevento in southern Italy. At the same time, however, I stress the limitations of studying texts in isolation, given that one region, city, or community could be simultaneously producing a number of different kinds of evidence, with possibly more than one view of sickness and healing. There is great potential for medical history in further investigation of the archaeological, liturgical, and charter evidence from early medieval Italy. The study of all surviving manuscripts from this period, not just medical words, can provide a bridge between the detailed examination of a particular text and a discussion of the wider literary and cultural traditions into which they fitted.


Production of a Novel Extracellular Polysaccharide by a Bacillus Strain Isolated from Soil.
A bacterium that was isolated from soil and identified as Bacillus circulans was found to produce a highly viscous extracellular polysaccharide when it was grown aerobically in a medium containing glucose as a sole source of carbon. The product was characterized by TLC and GC analyses as a novel heteropolysaccharide consisted of rhamnose, mannose, galactose, and mannuronic acid as sugar components. A maximal yield of polysaccharide reached about 2 g/liter by jar-fermentor culture at 30°C for 48 hr with a medium containing 1% glucose, 0.05% asparagine, 0.005% yeast extract, and small amounts of inorganic salts. Some culture conditions for the production of polysaccharide were investigated with flask culture; an optimal production was attained with a medium containing 0.1-1 % glucose and 0.01-0.05% asparagine, pH 7-8, at 30°C under aerobic conditions.