Can flowcytometric DNA studies forecast the prognosis of endometrial hyperplasia?
The study is investigating the relation of the ploidy pattern and cell cycle kinetics to different types of endometrial hyperplasia to select the high-risk women who will need strict follow up surveillance. An observational study of 152 patients with endometrial hyperplasia. Endometrial samples were subjected to flowcytometric study of the nuclear DNA content to determine the ploidy pattern and cell cycle kinetics. The mean age of women was 46.3+/-3.6 years. 15.8% of women were nulliparae, 36.8% were diabetic and 43.6% were hypertensive. 48.7% of women were obese (BMI>30). Most of endometrial samples (88.2%) were simple endometrial hyperplasia without atypia. The cell cycle kinetics in different types of endometrial hyperplasia shows that there were significant statistical differences as regards the S-phase fraction and proliferative index (PI) between typical and atypical hyperplasia. The study of cell cycle kinetics by flowcytometry might help in picking up, among all women with endometrial hyperplasia, the group of patients who need further close and strict follow up by endometrial pathologic study. This is going to minimize the cost and invasiveness of surveillance of patients with various grades of endometrial hyperplasia.


The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis.
Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. This study aims to systematically review the prevalence of cSVD in LMICs. Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.


Identification of Glycolaldehyde Enol (HOHC═CHOH) in Interstellar Analogue Ices.
Glycolaldehyde is considered the entry point in the aqueous prebiotic formose (Butlerow) reaction although it mainly exists in its unreactive hydrated form in aqueous solution. The characterization of the more reactive nucleophilic enol form under interstellar conditions has remained elusive to date. Here we report on the identification of glycolaldehyde enol (1,2-ethenediol, HOHC═CHOH) in low temperature methanol-bearing ices at temperatures as low as 5 K. Exploiting isotope labeling and isomer-selective photoionization coupled with reflectron time-of-flight mass spectrometry, our results unravel distinct reaction pathways to 1,2-ethenediol, thus demonstrating the kinetic stability, availability for prebiotic sugar formation, and potential detectability in deep space.


Induction of thymic lymphomas and squamous cell carcinomas following topic application of isopropyl methanesulfonate to female Hsd:(ICR)BR mice.
The goal of these experiments in female Hsd:(ICR)Br mice was to determine whether the direct-acting SN1 alkylating carcinogen isopropyl methanesulfonate (IMS) is carcinogenic and to compare its effects with those of the direct-acting SN2 methyl homologue, methyl methanesulfonate (MMS). The compounds were administered by topical application and s.c. injection. Analysis at the 288th day of mice receiving s.c. injections of IMS and MMS was the subject of a previous report (A. Segal et al., Proc. Soc. Exp. Biol. Med., 183: 132-135, 1986). The s.c. and topical application experiments were terminated at the 450th day and the final results are reported in this paper. In mice treated by s.c. injection with IMS, thymic lymphomas were observed in at least 20 of 32 mice, the first at the 40th day, and neoplasms were not observed at the injection site. Of the 30 MMS-treated mice, 11 developed sarcomas at the injection site and one thymic lymphoma was observed. In mice treated topically with IMS, thymic lymphomas were observed in 20 of 30 treated mice, the first at the 102nd day, and squamous cell carcinomas at the injection site were observed in 9 mice. Neither squamous cell carcinomas nor thymic lymphomas were observed in 30 mice following topical application of MMS. The direct-acting SN2 aklylating carcinogen beta-propiolactone was also administered by topical application. At the 450th day, at the same dose used for MMS (40 mumol/application), papillomas of the skin were observed in 25 of 30 treated mice, squamous cell carcinomas of the skin were seen in 17 mice, and one thymic lymphoma was observed. The results suggest that the rapid induction of thymomas by IMS may be related to its ability to alkylate exocyclic oxygen atoms in DNA of hemopoietic cells and also to a sensitivity of these cells to such lesions.


Treatment of gummy smile: Gingival recontouring with the containment of the elevator muscle of the upper lip and wing of nose. A surgery innovation technique.
The containment of the elevator muscle of the upper lip and wing of nose was used for the treatment of patients with gummy smile. This technique had corrected esthetic alterations of smile, reducing the upper lip elevation, which results in a smaller gingival display. An upper lip lengthening as well as a reduction in the upper lip shortening when the patient smiled could be observed. The high smile line was corrected without compromising the labial harmony. This study presents an innovative and effective therapeutic option to obtain a natural and harmonious smile. The patient expressed a high degree of satisfaction.


Use of beta-lactamase-producing anaerobes to prevent ceftriaxone from degrading intestinal resistance to colonization.
Six adult volunteers were given 1 g/d of intravenous ceftriaxone for 5 d (consecutive). Ceftriaxone and beta-lactamase activities were assayed in fecal samples obtained before and during drug administration, and anaerobic bacteria, Enterobacteriaceae, and fungi were counted. In two volunteers, no fecal beta-lactamase activity was detected, but ceftriaxone was present during treatment at concentrations of 1.8-2.0 mg/g of feces. Concomitantly, fecal counts of anaerobes in these volunteers dropped from 10.5 to less than 8 log10 colony-forming units (cfu)/g of feces, and those of Candida species increased more than 100-fold. However, in the feces of the four other volunteers, beta-lactamase activity was high during ceftriaxone administration, but no ceftriaxone was detected. In these volunteers, ceftriaxone administration was not followed by any significant change in counts of anaerobes or Candida species. This appeared to be due to the intraintestinal hydrolysis of ceftriaxone by resident beta-lactamase-producing anaerobes. In gnotobiotic mice associated with a human fecal flora containing no beta-lactamase-producing anaerobes, it was possible to prevent the deleterious effects of ceftriaxone on intestinal microbial composition and on colonization resistance (against a strain of Candida albicans and one of ceftriaxone-resistant Enterobacter cloacae) by feeding the animals with an association of four beta-lactamase-producing anaerobic strains.


The relationship of myelin basic protein (arginine) methyltransferase to myelination in mouse spinal cord.
The relationship between the activity of myelin basic protein (arginine) methyltransferase and myelination in the mouse spinal cord has been examined. The activity of this methylase increases between 8 and 45 days postnatal age and correlates well with other parameters of myelination. A comparison of myelin basic protein methylase with histone methylase activity during development indicates that each is a distinct, specific enzyme activity. Together, these results are considered to establish myelin based protein methylase as a myelination-related enzyme.


Frustrated rotator crystals and glasses of Brownian pentagons.
Two-dimensional Brownian dispersions of microscale pentagonal platelets exhibit rich structural and dynamical behavior as the particle area fraction, phi(A), is increased. As phi(A) is raised above 0.66, a rotator crystal forms, and while in an equilateral hexagonal lattice, pentagons still explore all angles as they rotationally diffuse. At larger phi(A), the interference of the tips of neighboring pentagons causes rotational dynamical heterogeneity; particle rotations become nonergodic, the hallmark of a frustrated rotator crystal. Upon further compression, the quenched-in rotational disorder and inability of pentagons to fully tile a flat plane creates spatial defects, precluding access to a dense striped crystalline packing.


Differential effects of glycosylated and non-glycosylated porcine prolactin on estradiol and progesterone secretion by rat granulosa cells in culture.
The objective was to better understand the interactions between prolactin and ovarian function. The effects of two variants of porcine prolactin (pPRL) on estradiol (E2) and progesterone (P4) production by rat granulosa cells in culture were studied using granulosa cells obtained from large preovulatory follicles of pregnant mare serum gonadotropin (PMSG)-treated immature Sprague-Dawley rats. Cultures were performed in the absence or presence of hCG (0.1 IU/ml) and different concentrations of either glycosylated and non-glycosylated (g-pPRL and ng-pPRL, respectively) pPRL. Dose-response studies showed that maximal stimulation occurred in all instances with g-pPRL at the dose of 10 ng/mL during the 72-h treatment period. In the case of E2, the maximal response was obtained in hCG-stimulated cultures, whereas the response of P4 was higher in cultures stimulated with g-pPRL in the absence of hCG. In a similar manner, the non-glycosylated form of pPRL increased, although to a lesser extent, the secretion of P4 only in those cultures incubated in the absence of hCG. In contrast to these observations, ng-pPRL was about twice as active than the glycosylated form on the stimulation of growth of Nb2 lymphoma cells. These data point out that glycosylation is involved in the differential effects of pPRL on ovarian steroidogenesis and support the role of carbohydrates in the structural-functional polymorphic nature of the hormone.


Bilateral Transverse Mandibular Second Molars: A Case Report.
Impaction of mandibular second permanent molars is a rare occurrence, with prevalence rates reported to be between 0.65% and 2.0%. In the absence of systemic conditions, impactions are usually unilateral. There appears to be no consensus as to the optimal treatment for impacted mandibular second molars and treatment plans will be based upon the individual case. Treatment may involve orthodontics and/or various surgical techniques, and early diagnosis is important. This paper presents an unusual case of bilateral transverse impaction of both mandibular second and third molars that was diagnosed at 18 years of age. All impacted molars were extracted.


Dental Implant Quality Register-A possible tool to further improve implant treatment and outcome.
The Board of EAO (European Association for Osseointegration) has discussed an initiative to explore the conditions to establish a Dental Implant Register. It was suggested to bring this issue to the EAO Consensus Conference 2018 for a discussion and to possibly propose relevant and manageable parameters. This article presents some select examples from quality registers in the medical field. Based on the experience of established registers, essentially in the medical field, factors considered to be of importance, if and when establishing a Dental Implant Register are introduced and discussed.


Fatal thrombotic microangiopathy in an infant with COVID-19: a case report.
While macrovascular thrombosis is common in adult COVID-19 patients, thrombotic microangiopathy as a part of endothelitis might play an important role in severe organ dysfunction. Thrombocytopenia-associated multiple organ failure (TAMOF) is a thrombotic microangiopathy syndrome that is associated with endothelial damage. Herein, we aim to report a pediatric TAMOF case related to SARS-CoV-2 infection which has been scarcely reported to date. A 7-month-old boy who became severely ill after being infected with SARS-CoV-2 required advanced critical care treatments such as continuous renal replacement therapy, therapeutic plasma exchange, and extracorporeal membrane oxygenation. A heart and lung biopsy obtained during sternotomy showed thrombotic microangiopathy. Despite early plasma exchange, mortality was inevitable because of severe liver failure. This case report implies that SARS-CoV-2 infection could cause TAMOF in children. To the best of our knowledge, this is the second SARS-CoV-2-induced pediatric TAMOF case. More studies are needed to determine alternative treatments for patients with TAMOF who are resistant to conventional therapies.


Cyclic topology in complex networks.
We introduce a cyclic coefficient R which characterizes the degree of circulation in complex networks. If a network has a perfect treelike structure, then R becomes zero. The larger value of R represents that the network has more cyclic structure. We measure both the cyclic coefficients and the distributions of local cyclic coefficients for various networks and discuss the cyclic structures of them.


[Chronic cervical and lumbar epidural catheterization through the atlanto-occipital membrane in rats].
We report here an efficient means of epidural catheter placement through atlanto-occipital membrane in rats. Male SD rats (n = 84) were divided into lumbar (n = 48) and cervical (n = 36) groups. Under sterile technique, PVC V-1 tubing was inserted and advanced caudally targeted to the C 4 or L 4 level. Analgesic efficacy and duration were measured by injecting increments of 2% lidocaine until a maximum paw withdrawal latency time from a radiant heat thermal stimulator. Rats (n = 6 each day) were sacrificed and an autopsy was performed to observe both the laterality of the catheter tip and the proliferation of fibrous tissue around the catheter. The volume of lidocaine and its duration was 52 +/- 17 microliters and 27 +/- 13 min (mean +/- SD) in lumbar, 30 +/- 10 microliters and 26 +/- 9 min in cervical group. In lumbar group, two catheters penetrated the dura. The remaining catheters were confirmed to be in the epidural space within L 4 +/- 1 or C 4 +/- 2 segment. Lumbar catheter tips were almost equally distributed between the center, left and right, while cervical catheter tips were distributed between left and center portion of the epidural space. The severity of tissue proliferation was time dependent. The proliferation of fibrotic tissue seemed more rapid in cervical than lumbar group. Although this approach for epidural catheter placement is efficient and produces excellent drug effects on day 3 after implantation, as reported by others, rapid development of fibrous tissue around the catheter quickly limits the usefulness of the epidural catheter.


Instrument for spatially resolved, temperature-dependent electrochemical impedance spectroscopy of thin films under locally controlled atmosphere.
We demonstrate an instrument for spatially resolved measurements (mapping) of electrochemical impedance under various temperatures and gas environments. Automated measurements are controlled by a custom LabVIEW program, which manages probe motion, sample motion, temperature ramps, and potentiostat functions. Sample and probe positioning is provided by stepper motors. Dry or hydrated atmospheres (air or nitrogen) are available. The configurable heater reaches temperatures up to 500 °C, although the temperature at the sample surface is moderated by the gas flow rate. The local gas environment is controlled by directing flow toward the sample via a glass enclosure that surrounds the gold wire probe. Software and hardware selection and design are discussed. Reproducibility and accuracy are quantified on a Ba(Zr,Y)O3-δ proton-conducting electrolyte thin film synthesized by pulsed laser deposition. The mapping feature of the instrument is demonstrated on a compositionally graded array of electrocatalytically active Ba(Co,Fe,Zr,Y)O3-δ thin film microelectrodes. The resulting data indicate that this method proficiently maps property trends in these materials, thus demonstrating the reliability and usefulness of this method for investigating electrochemically active thin films.


Electrical correlates of mechanical events in the cochlea.
In this paper the main emphasis is laid on presenting an up-to-date description of the relationships between stimulus-related cochlear potentials: cochlear microphonic (CM) and summating potential (SP) and the preceding mechanical events. To this end, CM and SP (both DIF and AVE SP) magnitude functions, obtained with the differential electrode technique, are shown from various turns of the guinea pig's cochlea as recorded at a constant stapes displacement. The similarity between these curves and corresponding basilar membrane displacement functions is considered. The influence upon CM recording of the distributed nature of the generators, as well as the presence of strong nonlinear effects is discussed.


[A toddler with traumatic brain injury].
A 14-month-old boy presented with a haematoma and an oedematous swelling in the left parieto-occipital region after sustaining a fall from 3 meters. CT images of the brain showed a multifragmentary fracture in the parietotemporal region. Because the swelling progressed during admission, an MRI of the brain was performed, which revealed extrusion of brain tissue through a skull defect into the subgaleal space. Resultantly, the diagnosis of 'cranial burst fracture' was established. After neurosurgical resection and dural repair, the boy was discharged from the hospital without neurological symptoms.


Fresh decellularized versus standard cryopreserved pulmonary allografts for right ventricular outflow tract reconstruction during the Ross procedure: a propensity-matched study.
Recent studies have shown favourable early results with decellularized allografts (DAs) for right ventricular outflow tract reconstruction during the Ross procedure. However, mid- and long-term outcome data are still scarce. The objective of this study was to compare the durability of fresh DAs with standard cryopreserved allografts (SCAs) in patients undergoing the Ross procedure. Two hundred patients underwent the Ross procedure with DA and 202 with SCA. Using propensity score matching, mid- and long-term clinical outcome and echocardiographic allograft function over time were compared. One hundred and thirty DA patients (median age 28 years, 71.5% men, mean follow-up 4.2 ± 2.6 years) were matched with 130 SCA patients (median age 30 years, 69.2% men, mean follow-up 13 ± 4.5 years). After matching, there were no differences in baseline characteristics. In the matched DA vs SCA groups, actuarial 8-year freedom from allograft dysfunction (DA = 86.7% vs SCA = 87.3%, P = 0.183) and freedom from allograft reintervention (DA = 99.2% vs SCA = 97.6%, P = 0.642) were comparable. Longitudinal echocardiographic analyses showed a significantly lower progression rate of peak right ventricular outflow tract gradients in the DA group during the first 3 years after the operation. Absolute gradients over time were slightly lower in DA when compared with SCA, although 95% confidence intervals overlapped. Up to 8 years of follow-up, DA and SCA used for right ventricular outflow tract reconstruction in the Ross procedure are associated with comparably excellent clinical and haemodynamic outcome. Longer follow-up and dedicated echocardiographic studies are still necessary to confirm the long-term performance of the DAs.


Glucose-insulin-potassium therapy in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials.
Glucose-insulin-potassium (GIK) has been advocated in the setting of acute coronary syndrome (ACS) to reduce ischemia-related arrhythmias and myocardial injury. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess whether the use of GIK infusions >3 or <3 hours after the onset of symptoms reduce mortality or cardiac arrest. Electronic databases (Medline, EMBASE, and Cochrane Central Register of Controlled Trials) and references of retrieved articles were searched for RCTs evaluating the effect of GIK infusions, <3 hours or >3 hours after the onset of symptoms, on mortality and/or cardiac arrest. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each outcome. Nine trials were identified and eligible for review. The summary OR for in-hospital mortality was 1.01 (95% CI 0.94 to 1.09), based on 2,542 deaths among 27,294 patients. The subgroup analysis according to the study enrollment time (within 3 hours [OR, 0.77, 95% CI 0.50-1.16], vs. >3 hours [OR, 0.90; 95% CI, 0.67-1.21]) did not reveal any difference in mortality. Administration of GIK in ACS patients does not significantly reduce mortality whether or not GIK administration >3 or <3 hours after the onset of symptoms.


Heart failure and mitochondrial dysfunction: the role of mitochondrial fission/fusion abnormalities and new therapeutic strategies.
The treatment of heart failure (HF) has evolved during the past 30 years with the recognition of neurohormonal activation and the effectiveness of its inhibition in improving the quality of life and survival. Over the past 20 years, there has been a revolution in the investigation of the mitochondrion with the development of new techniques and the finding that mitochondria are connected in networks and undergo constant division (fission) and fusion, even in cardiac myocytes. This has led to new molecular and cellular discoveries in HF, which offer the potential for the development of new molecular-based therapies. Reactive oxygen species are an important cause of mitochondrial and cellular injury in HF, but there are other abnormalities, such as depressed mitochondrial fusion, that may eventually become the targets of at least episodic treatment. The overall need for mitochondrial fission/fusion balance may preclude sustained change in either fission or fusion. In this review, we will discuss the current HF therapy and its impact on the mitochondria. In addition, we will review some of the new drug targets under development. There is potential for effective, novel therapies for HF to arise from new molecular understanding.


Pulse compression in a time variant system with application to ultrasonic vibrometry.
Pulse compression is normally applied only to time-invariant systems, as the variation of a system's properties during its interrogation violates assumptions of the compression process. However, there is an exact solution to the pulse-compression problem when the time variance satisfies two criteria, which are the same as those required for the operation of an ultrasonic vibrometer in the context of a tissue elastography system. One is that the variations be very small in comparison with the wavelength of the interrogating ultrasound. The other is that the bandwidth of the variations be within one Nyquist band as sampled by the periodic interrogation signal. The solution to this problem involves a step-wise interpolation of the static pulse-compression transfer function in the frequency domain. This technique, in conjunction with the selection of an appropriate interrogation signal, offers significant advantages in measurement time or measurement resolution for an ultrasonic vibrometer limited by additive noise at the receiver. The characteristics of optimal interrogation signals for this technique are the signal's crest factor, spectral energy distribution, and phasing. These relate to the intended compression pulse, the noise, and the static response of the system. The technique has been demonstrated analytically, experimentally, and with numerical models.


Remote Ischemic conditioning as an emerging tool to improve corticospinal transmission in individuals with chronic spinal cord injury.
Remote ischemic conditioning (RIC) involves transient blood flow restriction to one limb leading to systemic tissue-protective effects. RIC shares some potential underlying mechanisms with intermittent hypoxia (IH), in which brief bouts of systemic hypoxia trigger increases in growth factor expression and neural plasticity. RIC has shown promise in acute myocardial infarction and stroke but may be applicable toward chronic neuropathology as well. Consequently, this review discusses similarities and differences between RIC and IH and presents preliminary and ongoing research findings regarding RIC. Several publications demonstrated that combining RIC with motor training may enhance motor learning in adults with intact nervous systems, though the precise mechanisms were unclear. Our own preliminary data has found that RIC, in conjunction with task specific exercise, can increase corticospinal excitability in a subset of people without neurological injury and in those with chronic cervical spinal cord injury or amyotrophic lateral sclerosis. RIC is a low-cost intervention easy to deliver in a clinical or home setting. Its potential application to facilitate neural plasticity and motor learning during rehabilitation training for individuals with chronic neurological disorders is a novel concept requiring further investigation to characterize mechanisms, safety, and efficacy.


Attentional impairments following right hemisphere damage with and without hemispatial neglect: A comparative study.
This study aimed to evaluate the performance of patients with right hemisphere damage (RHD) with or without hemispatial neglect (HN) on a cancellation task. The study involved 31 control participants and 31 patients with RHD, matched by age, education, and frequency of reading and writing habits. The numbers of omission and random errors as well as the mean time to task completion were compared between adults with and without RHD, as well as between patients with and without HN. The latter made more left-sided omission errors, and more overall omission errors, than patients with RHD and no HN. The location of the first target canceled differed between subjects with RHD and control participants, as well as between patients with and without hemineglect. The use of organized vs. disorganized search strategies did not differ between groups. Further studies are required to investigate the performance of patients with HN of different levels of severity.


Brain metastasis from large cell neuroendocrine carcinoma of the urinary bladder.
In patients with urinary bladder cancer, brain metastases are quite rare and occur in only 1-7% of these patients. Of the urinary bladder cancers, large cell neuroendocrine carcinoma (LCNEC) is extremely rare; only 16 cases have been reported to date. In this report, a case of brain metastasis from LCNEC of the urinary bladder is described. A 74-year-old man was admitted with confusion and left-sided hemiparesis. Head magnetic resonance imaging demonstrated a ring-enhancing lesion in the right frontal lobe. Whole body computed tomography revealed a suspicious lesion in the urinary bladder. These findings were considered consistent with metastatic brain tumor. Craniotomy and tumor removal were performed. After craniotomy, the patient underwent cystoscopy and the bladder mass was biopsied. Histological and immunohistochemical examination of both the brain tumor and bladder mass revealed LCNEC. According to these findings, the patient was diagnosed with a brain metastasis from LCNEC of the urinary bladder. To our knowledge, this is the first report of a patient with a brain metastasis from LCNEC of the urinary bladder.


Molecular insights into insulin action and secretion.
Tightly co-ordinated control of both insulin action and secretion is required in order to maintain glucose homeostasis. Gene knockout experiments have helped to define key signalling molecules that affect insulin action, including insulin and insulin-like growth factor-1 (IGF-1) receptors, insulin receptor substrate (IRS) proteins and various downstream effector proteins. beta-cell function is also a tightly regulated process, with numerous factors (including certain signalling molecules) having an impact on insulin production, insulin secretion and beta-cell mass. While signalling molecules play important roles in insulin action and secretion under normal circumstances, abnormal insulin signalling in muscle, adipose tissue, liver and pancreas leads to insulin resistance and beta-cell dysfunction. In particular, the signalling protein IRS-2 may have a central role in linking these abnormalities, although other factors are likely to be involved.


Anticancer Activity of Dendriplexes against Advanced Prostate Cancer from Protumoral Peptides and Cationic Carbosilane Dendrimers.
The interaction of neuropeptides, vasoactive intestinal peptide (VIP), or growth hormone-releasing hormone (GHRH), with a cationic carbosilane dendrimer forms dendriplexes with antitumoral behavior in advanced prostate cancer cells PC3. At the concentrations used for dendriplexes formation, the free peptides were protumoral and prometastatic in advanced prostate cancer, while dendrimer only showed low cytotoxicity, but did not avoid the metastatic behavior of PC3 cells. However, these nanoplexes favored also cell adhesion and avoided cell migration. Also, the dendriplexes were not toxic for no tumoral prostate cells (RPWE-1) or fibroblasts. The use of labeled GHRH peptide (rhodamine labeled) and a dendrimer (fluorescein labeled) allowed us to observe that both systems reach the intracellular milieu after dendriplex formation. The treatment of PC3 cells with the nanoplexes reduced expression of vascular endothelial growth factor (VEGF) and cyclic adenosine monophosphate (cAMP). Molecular modeling analysis highlights the important contribution of the carbosilane framework in the stabilization of the dendriplex, since dendrimer interacts with a peptide region where hydrophobic amino acids are presented.


Posttranslational regulation of TCR Valpha allelic exclusion during T cell differentiation.
We have previously shown that phenotypic allelic exclusion of TCR alpha-chain is functional only in mature thymocytes. A significant proportion of immature thymocytes (TCRlow) express more than one cell surface alpha-chain, but mature thymocytes (TCRhigh) show phenotypic allelic exclusion and express only a single alpha-chain. We have analyzed thymocytes for both surface and intracellular alpha-chain expression and find that the majority of mature thymocytes express a second alpha-chain intracellularly. This result is predicted by a model in which the developmentally regulated allelic exclusion of the TCR alpha-chain is caused by competition between alpha-chains for the beta-chain rather than by models in which one alpha-chain is down-regulated or in which selection favors cells with only a single alpha-chain species. Changes in the relative amounts of alpha- and beta-chains available for pairing may therefore allow competition between the two alpha-chains for the beta-chain. Peripheral T cells also frequently express second alpha-chains in the cytoplasm (18-27%), despite a rather low frequency of dual alpha-chain expression on the cell surface (2-4%). The frequency of nonsurface expressed alpha-chains is reduced somewhat compared with thymocytes, indicating that an additional level of control of allelic exclusion operates during the maturation of peripheral T cells.


[Repetitive movements of the upper limbs: results of exposure evaluation and clinical investigation in the manual sanding of wood in the Valdichiana region].
The aim of this study was to evaluate the level of risk exposure deriving from repetitive movements of the upper limbs, among a population of female workers manually sand papering timber products. The study also included an anamnestic and clinical assessment for the purpose of detecting and diagnosing WMSDs in the study population. The authors report a distinct prevalence of such disorders among the female workers exposed to a high level of risk, also in view of the total absence of recovery periods.


[Follow-up of elderly patients with fractures. Results of a catamnestic study of patients with femoral-(neck-)fractures].
A random sampling of n = 30 patients with fractures of the (neck of the) femur was followed up approx. 1 year after surgery, early mobilisation and rehabilitation. The average age was 79 years. The follow-up revealed a noticeable decrease in independence compared to the status at the time of discharge from hospital. This is in part due to health but mainly due to mental, social and organisational factors. The results agree with the assumption that the potential gained during the inpatient treatment period may be relatively invalidated during the subsequent outpatient phase unless measures are taken to ensure long-term quality assurance. This preservation of quality involves, among other factors, in particular satisfactorily exhaustive information and guidance of the patient and his relatives (by giving competent medical advice), clarification of the domestic situation already during the inpatient period, and cooperation with all aftercare institutions including the next of kin.


Essential skills for baccalaureate graduates: perspectives of education and service.
What psychomotor tasks should baccalaureate graduates be able to perform when they arrive on the doorsteps of practice settings? This article describes a research study in which a representative sample of nursing educators and nursing service personnel provide their perceptions in regard to that question. The content offers a clear view of the expectations of both groups, emphasizes the need for dialogue on this topic between educational service, and raises important issues for nursing administrators regarding the role of staff development and the transition of new graduates to the work setting.


Biomechanical evaluation of kyphoplasty with calcium sulfate cement in a cadaveric osteoporotic vertebral compression fracture model.
Vertebral compression fractures can cause deformity, pain, and disability. Kyphoplasty involves percutaneous insertion of an inflatable balloon tamp into a fractured vertebra followed by injection of polymethylmethacrylate (PMMA) bone cement. PMMA has several disadvantages such as potential thermal necrosis and monomer toxicity. Calcium sulfate cement (CSC) is nontoxic, osteoconductive, and bioabsorbable. To evaluate the biomechanical performance of CSC for kyphoplasty in cadaveric osteoporotic vertebral bodies. Destructive biomechanical tests using fresh cadaveric thoracolumbar vertebral bodies. Thirty-three vertebral bodies (T9 to L4) from osteoporotic cadaveric spines were disarticulated, stripped of soft tissue, and measured for height and volume. Each vertebral body was compressed at 0.5 mm/s using a hinged plating system on a materials testing machine to create an anterior wedge fracture and reduce the anterior height by 25%. Pretreatment strength and stiffness were measured. Two KyphX inflatable balloon tamps were used to reexpand each vertebral body. After randomization, three groups were created: Group A-no cement; Group B-PMMA; Group C-calcium sulfate cement. Groups B and C were filled with the corresponding cement to 25% of the vertebral body volume. All vertebral bodies were then recompressed by 25% of the post-kyphoplasty anterior height to obtain posttreatment strength and stiffness. Treatment with PMMA restored vertebral strength to 127% of the intact level (4168.2 N+/-2288.7) and stiffness to 70% of the intact level (810.0 N/mm+/-380.6). Treatment with CSC restored strength to 108% of the intact level (3429.6 N+/-2440.7) and stiffness to 46% of the intact level (597.7 N/mm+/-317.5). CSC and PMMA were not significantly different for strength restoration (p=.4). Significantly greater strength restoration was obtained with either PMMA or CSC, compared with the control group (p=.003 and .03, respectively). Stiffness restoration tended to be greater with PMMA than for CSC, but this difference was not statistically significant (p=.1). Both cements had significantly greater stiffness when compared with the control group (p=.001 and p=.04, respectively). Use of CSC for kyphoplasty yields similar vertebral body strength and stiffness as compared with PMMA. It may be a useful alternative bone cement for kyphoplasty. Further studies are required to assess the bioabsorption of CSCs after kyphoplasty in vivo.


The V kappa IIIb light chain sub-subgroup. II. Isotype expression in acquired hypogammaglobulinaemia and as a function of age.
The V kappa IIIb sub-subgroup of the human immunoglobulin V kappa III light chain subgroup has at least two unique properties. First, some IgM monoclonal autoantibodies, in particular cryoprecipitable anti-IgG (Kunkel et al., 1974; Ledford et al., 1983), anti-low density lipoprotein (Ledford et al., 1983) and certain cold agglutinin (Feizi et al., 1976) antibodies predominantly contain V kappa IIIb light chains. Second, in normal adult human serum, V kappa IIIb comprises approximately 25% of the IgM but less than 0.4% of the IgG or IgA kappa-chain pools (Moynihan, Looney & Abraham, 1985). Studies have suggested an altered regulation of IgM, IgG, and IgA-V kappa IIIb in some patients with acquired hypogammaglobulinaemia, a heterogeneous group of immunodeficiencies with low serum levels of Ig. An increase in the serum levels of V kappa IIIb light chains has been noted in some of these patients (Solomon & Mclaughlin, 1969) which is apparently due to elevated levels of light chains of the V kappa IIIb sub-subgroup (Greenstein & Abraham, 1984). However, the isotype association of V kappa IIIb in these patients has not been determined. In order to clarify whether the noted increase in V kappa IIIb levels is due to its selective expression with IgM or to an abnormality of immunoregulation, the heavy chain isotypes associated with V kappa IIIb light chains have been determined in a previously studied group of adults with acquired hypogammaglobulinaemia (Greenstein & Abraham, 1984). Further, the isotype distribution of V kappa IIIb light chains in another group of functional, albeit transient, hypogammaglobulinaemics (i.e. normal neonates) has also been studied by measuring IgM-V kappa IIIb levels in cord blood, and compared to the V kappa IIIb serum levels found in aged adults (mean age 75 years).


Influence of different oxygen modes on the blood oxygen transport and prooxidant-antioxidant status during hepatic ischemia/reperfusion.
Oxygen supply was corrected in rabbits during the hepatic ischemia/reperfusion by means of different breathing mixtures: hypoxic (14.8 % O(2)+85.2 % N(2)), hyperoxic (78 % O(2)+20.2 % N(2)+ 1.8 % CO(2)), or hypercapnic (5 % CO(2) in air). Hepatic ischemia was induced for 30 min by ligation of hepatic artery, reperfusion period lasted 120 min. Indices of blood oxygen transport (p50(act), pCO(2), pH, pO(2), etc.) and prooxidant-antioxidant balance (Schiff bases, conjugated dienes, catalase, retinol, alpha-tocopherol) were measured in the blood and liver. The severity of reperfusion damage was evaluated by the activities of alanine and aspartate aminotransferases (ALT, AST) in the blood. Hepatic ischemia/reperfusion resulted in higher p50(act) in hepatic venous and mixed venous blood in all experimental groups. The changes of p50(act) were most marked in the hypercapnic group and were the weakest in the hypoxic group. The rise in p50(act) was accompanied by higher levels of lipid peroxidation products, ALT and AST in blood and liver homogenates, and by a simultaneous fall of alpha-tocopherol and retinol concentrations, except in the hypoxic group. Catalase activity at the end of reperfusion increased under normoxia, decreased under hyperoxia or hypercapnia and did not change under hypoxia. The moderate hypoxia during reperfusion was accompanied by a better balance between the mechanisms of reactive oxygen species production and inactivation that may be observed by optimal changes in p50act and reduced the hepatic damage in this pathological condition.


ACR Appropriateness Criteria® Occupational Lung Diseases.
Ordering the appropriate diagnostic imaging for occupational lung disease requires a firm understanding of the relationship between occupational exposure and expected lower respiratory track manifestation. Where particular inorganic dust exposures typically lead to nodular and interstitial lung disease, other occupational exposures may lead to isolated small airway obstruction. Certain workplace exposures, like asbestos, increase the risk of malignancy, but also produce pulmonary findings that mimic malignancy. This publication aims to delineate the common and special considerations associated with occupational lung disease to assist the ordering physician in selecting the most appropriate imaging study, while still stressing the importance of a multidisciplinary approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Embryonal tumors with multilayered rosettes in children: the SFCE experience.
The purpose of this study was to retrospectively study embryonal tumors with multilayered rosettes (ETMR), a rare new entity that gathers ETAN-TR (embryonal tumor with abundant neuropil and true rosettes), ependymoblastomas, and medulloepitheliomas, in order to improve their descriptions and try to better define therapeutic modalities. Patients with ETMR, ETAN-TR, ependymoblastoma, and medulloepithelioma treated in SFCE centres (Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'adolescent) since 2000 were collected. Data were retrieved from clinical charts. Thirty-eight patients were included in the analysis. Seventeen had an ETAN-TR, 13 had a medulloepithelioma, and 8 had an ETMR. No ependymoblastoma was included. The median age at diagnosis was 31 months (range, 2.8-141 months). The predominant tumor location was supratentorial (66%); 18.4% patients had metastatic lesion. LIN28A expression was positive in 11/11 patients. Amplification of the locus 19q13.42 was positive in 10/12 patients. Thirty patients were treated according to the primitive neuroectodermal tumors of high risk (PNET-HR) protocol. The median time of follow-up was 0.9 years (range 0.1 to 15.3 years). The 1-year event-free survival (EFS) and overall survival (OS) were, respectively, 36% CI 95% (23-55) and 45% CI 95% (31-64). On multivariate analysis, complete surgical resection, radiotherapy, and high-dose chemotherapy were associated with a better overall survival with a relative risk of, respectively, 7.9 CI 95% (2.6-23.5) p < 0.0002, 41.8 CI 95% (9.4-186) p < 0.0001, and 3.5 CI 95% (1.3-9.5) p = 0.012. Prognosis of ETMR remains dismal despite multimodal therapy. LIN28A immunostaining and 19q13.42 amplification should be systematically done to secure the diagnosis. Complete surgical resection, radiotherapy, and high-dose chemotherapy are associated with better outcome.


PtAl truncated octahedron nanocrystals for improved formic acid electrooxidation.
We successfully obtained truncated octahedron PtAl alloy nanocrystals (∼10 nm) via a facile one-pot strategy. The PtAl nanocrystals exhibited enhanced activity in formic acid electrooxidation compared to commercial Pt/C, which could be ascribed to the large density of defects on the surface as well as the synergy between Pt and Al.


Books helpful to patients with sexual and marital problems.
Providing patients with helpful and timely resource materials requires clinicians to be familiar with an ever-changing and over-whelmingly large body of information. To assist clinicians in the task of assembling current useful materials, we surveyed members of the Society for Sex Therapy and Research by mail and an electronic listserve. The survey forms requested respondents to list books, videotapes, and Internet sites that they recommended to their patients with specific sexual/marital problems. Fifty-two of 216 surveys were returned for a response rate of 24%. Responses were included if they were cited at least three times. Each citation was verified for accuracy and developed into an acceptable journal-quality reference. Frequency counts for responses were calculated, and a bibliography was developed.


The use of small malleable endoscopes to assess pedicle screw placement: technical note.
Because the improper insertion of pedicle screws can be associated with significant neurologic morbidity, attempts are being made to improve on the accuracy of pedicle screw placement. As a possible strategy we have studied the use of small malleable endoscopes to explore the pedicle and exiting nerve root during and after pedicle screw placement. These small endoscopes are 1.2 mm in diameter and can be bent so that the superior, medial and inferior walls of the pedicle can be visualized. Additionally, the nerve roots superior to and inferior to the pedicle can be seen throughout their entire intraspinal course. Using these endoscopes in ten patients requiring the placement of forty-four pedicle screws we were able to visualize the pedicles and nerve roots in all cases. The endoscope demonstrated that one screw had penetrated the inferior cortex of the pedicle. This penetration was not palpable with blind probing of the pedicle and foramina. These cases suggest that this simple technique may be of use in limiting improper pedicle screw placement.


Early-Life Nutrition in Preterm Infants and Risk of Respiratory Infections and Wheezing: A Scoping Review.
Preterm birth is a common early-life event that can lead to long-term consequences. The incidence of wheezing, asthma, and respiratory tract infections is higher in children born prematurely than in the general population. The purpose of this review was to synthesize the existing literature on the role of early-life nutrition in the later risk of respiratory morbidities. A scoping review of the literature was performed by searching three online databases. Inclusion criteria were: infants born <37 GWk, comparing human milk versus any other type of milk feeding formulation. Our primary outcomes were wheezing or asthma or respiratory tract infections after discharge. Two authors independently screened the results and extracted study characteristics using a predefined charting form. Nine articles were included (eight cohort studies and one randomized trial). Four studies supported the protective effect of breastfeeding on wheezing or respiratory infections or both. Four studies did not confirm this association. One study confirmed the protective role of breastfeeding only on the subgroup of girls. There was a high heterogeneity among the included studies, in the type of milk feeding, outcomes, and age at follow-up. The current evidence is conflicting. The high heterogeneity and methodological flaws could have influenced the results of the studies. Carefully designed studies are required to define the role of early-life nutrition among preterm infants on their long-term respiratory outcomes.


Development of a Selective Medium for the Fungal Pathogen Fusarium graminearum Using Toxoflavin Produced by the Bacterial Pathogen Burkholderia glumae.
The ascomycete fungus Fusarium graminearum is a major causal agent for Fusarium head blight in cereals and produces mycotoxins such as trichothecenes and zearalenone. Isolation of the fungal strains from air or cereals can be hampered by various other airborne fungal pathogens and saprophytic fungi. In this study, we developed a selective medium specific to F. graminearum using toxoflavin produced by the bacterial pathogen Burkholderia glumae. F. graminearum was resistant to toxoflavin, while other fungi were sensitive to this toxin. Supplementing toxoflavin into medium enhanced the isolation of F. graminearum from rice grains by suppressing the growth of saprophytic fungal species. In addition, a medium with or without toxoflavin exposed to wheat fields for 1 h had 84% or 25%, respectively, of colonies identified as F. graminearum. This selection medium provides an efficient tool for isolating F. graminearum, and can be adopted by research groups working on genetics and disease forecasting.


Statistical considerations in long-term efficacy evaluation of anti-cancer therapies.
Anti-cancer therapy has been a significant focus of research. Developing and marketing various types and mechanisms of anti-cancer therapies benefit a variety of patients significantly. The long-term benefit to patients in evaluating the risk-benefit ratio of anti-cancer therapy has become a significant concern. This paper discusses the evaluation of long-term efficacy within the estimand framework and summarizes the various strategies for addressing potential intercurrent events. Non-proportional hazards of survival data may arise with novel anti-cancer therapies, leading to potential bias in conventional evaluation methods. This paper reviews statistical methods for addressing this issue, including novel endpoints, hypothesis testing, and efficacy estimation methods. We also discuss the influences of treatment switching. Although advanced methods have been developed to address the non-proportional hazard, they still have limitations that require continued collaborative efforts to resolve issues.


Complete nucleotide sequences of two NDM-1-encoding plasmids from the same sequence type 11 Klebsiella pneumoniae strain.
The sequence type 11 Klebsiella pneumoniae strain Kpn-3002cz was confirmed to harbor two NDM-1-encoding plasmids, pB-3002cz and pS-3002cz. pB-3002cz (97,649 bp) displayed extensive sequence similarity with the blaNDM-1-carrying plasmid pKPX-1. pS-3002cz (73,581 bp) was found to consist of an IncR-related sequence (13,535 bp) and a mosaic region (60,046 bp). A 40,233-bp sequence of pS-3002cz was identical to the mosaic region of pB-3002cz, indicating the en bloc acquisition of the NDM-1-encoding region from one plasmid by the other.


Thrombolytic therapy during cardiopulmonary resuscitation.
Recently, efforts have been undertaken to investigate the effects of thrombolysis during cardiopulmonary resuscitation (CRP) in patients suffering from massive pulmonary embolism or acute myocardial infarction. In up to 70% of patients with cardiac arrest, one of these two diseases is the underlying cause of deterioration. Nevertheless, thrombolysis has not been conducted during CPR because of the fear of severe bleeding complications. However, an increasing number of clinical studies suggest that thrombolytic therapy during CPR can contribute to haemodynamic stabilisation and survival in patients with massive pulmonary embolism and acute myocardial infarction, when conventional CPR procedures have been performed unsuccessfully. Apart from the specific causal action of thrombolytic agents at the site of pulmonary emboli and coronary thrombosis, experimental data indicate that thrombolysis during CPR can improve microcirculatory reperfusion, which may be most important in the brain. In accordance with these data, marked activation of blood coagulation without adequate activation of endogenous fibrinolysis has been demonstrated early after cardiac arrest. In summary, thrombolysis during CPR is presently a treatment strategy that can be performed on an individual basis in patients with pulmonary embolism or acute myocardial infarction. It may become a routine measure if positive results of randomised, controlled clinical trials will be available in the future.


Racial Differences in the Effects of Neighborhood Disadvantage on Residential Mobility in Later Life.
Past research on the residential mobility of older adults has focused on individual-level factors and life course events. Less attention has been paid to the role of the residential environment in explaining residential mobility in older adults. We sought to understand whether neighborhood disadvantage had predictive utility in explaining residential relocation patterns, and whether associations differed between Whites and non-Whites. Data are from the National Social Life, Health and Aging Project, a nationally representative sample of community-dwelling older adults. Neighborhoods were defined at the census tract level. Local movers (different census tract, same county) and distant movers (different county) were compared with stayers. After adjusting for individual-level factors, neighborhood disadvantage increased the likelihood of a local move, regardless of race/ethnicity. For non-Whites, higher neighborhood disadvantage decreased the likelihood of a distant move. Among local movers, Blacks and Latinos were less likely to improve neighborhood quality than Whites. Neighborhood disadvantage may promote local mobility by undermining person-environment fit. Racial differences in access to better neighborhoods persist in later life. Future research should explore how older adults optimize person-environment fit in the face of neighborhood disadvantage when the possibility of relocation to a better neighborhood may be restricted.


The effect of shoulder immobilization on balance in community-dwelling older adults.
Shoulder immobilization devices are commonly used in the treatment of older adults following proximal humeral fractures. Immobilization of the shoulder may have a negative effect on balance, which could increase risk for falls. The purpose of this study was to examine the effect of shoulder immobilization on balance in the community-dwelling older adult population as measured by the Berg Balance Scale (BBS). Fifty-three subjects (14 men and 39 women, mean age = 75.4 years) participated in the study. The BBS was administered twice to each participant. Subjects were tested once while wearing a shoulder immobilizer and once without a shoulder immobilizer. The immobilizer positioned the elbow at 90 degrees of flexion and anchored the arm to the trunk. The Wilcoxon signed-ranks test was used to evaluate differences in BBS scores. A 2-tailed test was performed with a set at .05. Mean (SD) BBS scores were 53 (4.0) without the immobilizer and 52 (4.7) with the immobilizer. BBS change scores (score with immobilizer minus score without immobilizer) ranged from +1 to -7, with a mean change score of -1.02. The Wilcoxon signed-ranks test indicated a significant difference between paired observations (negative ranks = 29, positive ranks = 6, P < .0001). Balance was impaired (significantly lower BBS scores) when subjects wore the device compared with the testing sessions without the device. The results indicate that immobilizing the shoulder may have a negative effect on balance as measured by the BBS. If shoulder immobilization places an individual at greater risk for falls, early balance screening by a physical therapist to determine the appropriateness of a fall prevention program may be indicated.


Modeling the biological response of normal human cells, including repair processes, to fractionated carbon beam irradiation.
To understand the biological response of normal cells to fractionated carbon beam irradiation, the effects of potentially lethal damage repair (PLDR) and sublethal damage repair (SLDR) were both taken into account in a linear-quadratic (LQ) model. The model was verified by the results of a fractionated cell survival experiment with normal human fibroblast cells. Cells were irradiated with 200-kV X-rays and monoenergetic carbon ion beams (290 MeV/u) at two irradiation depths, corresponding to linear energy transfers (LETs) of approximately 13 keV/μm and 75 keV/μm, respectively, at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. When we only took into account the repair factor of PLDR, γ, which was derived from the delayed assay, the cell survival response to fractionated carbon ion irradiation was not fully explained in some cases. When both the effects of SLDR and PLDR were taken into account in the LQ model, the cell survival response was well reproduced. The model analysis suggested that PLDR occurs in any type of radiation. The γ factors ranged from 0.36-0.93. In addition, SLD was perfectly repaired during the fraction interval for the lower LET irradiations but remained at about 30% for the high-LET irradiation.


Characterization of γδ T cells in patients with non-small cell lung cancer.
Systemic immune defects that are associated with disease progression exist in a variety of malignancies. γδ T cells are innate-like lymphocytes that do not require self-major histocompatibility complex-restricted priming. Ex vivo-expanded circulating γδ T cells exhibit promising antitumor activity and are a potential candidate for the treatment of various malignancies, including non-small cell lung cancer (NSCLC). In the present study, flow cytometry was used as a method to study the phenotypes and characteristics of γδ T cells. A lower frequency of circulating γδ T cells was observed in NSCLC patients than in healthy controls. In advanced NSCLC patients, γδ T cells were also detected in the pleural effusion, but the frequency of γδ T cells here was significantly lower than in the peripheral blood. Vδ1+and Vδ1-Vδ2- T cells represented the most enriched subsets in the pleural effusion. Moreover, the present study demonstrated that Vδ1+ T cells are a type of γδ T cells characterized by a cluster of differentiation (CD)3dim T-cell receptor (TCR)γδbright phenotype, whereas Vδ2+ T cells represent a CD3brightTCRγδdim phenotype, according to the fluorescence intensity of CD3 and γδTCR using flow cytometry. Finally, the present study reported a decrease in the expression of CD27 and CD28 molecules on the surface of circulating γδ T cells in NSCLC. The present data suggest the existence of a dysregulated repertoire of γδ T cells in NSCLC, which exhibit impaired activation and a reformed cytokine-releasing profile. Although the ex vivo expansion of γδ T cells may be a prospective therapeutic strategy in NSCLC patients, it remains necessary to clarify which subsets (Vδ1 or Vδ2) should be expanded and the sources from which γδ T cells should be generated.


Analysis of clinical data and T helper 1/T helper 2 responses in patients with different clinical forms of leprosy.
Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.


The combined role of catalysis and solvent effects on the Biginelli reaction: improving efficiency and sustainability.
The traditional Biginelli reaction is a three-component condensation between urea, benzaldehyde and an acetoacetate ester to give a dihydropyrimidinone. An investigation into catalytic and solvent effects has returned the conclusion that the diketo-enol tautomerisation equilibrium of the dicarbonyl reactant dictates the yield of the reaction. Whereas the solvent is responsible for the tautomerisation equilibrium position, the catalyst only serves to eliminate kinetic control from the reaction. Generally, to preserve reaction efficiency and improve sustainability, bio-derivable p-cymene was found to be a useful solvent. The metal-enolate intermediate that results from the application of a Lewis acidic catalyst often cited as promoting the reaction appears to hinder the reaction. In this instance, a Brønsted acidic solvent can be used to return greater reactivity to the dicarbonyl reagent.


ModelTeller: Model Selection for Optimal Phylogenetic Reconstruction Using Machine Learning.
Statistical criteria have long been the standard for selecting the best model for phylogenetic reconstruction and downstream statistical inference. Although model selection is regarded as a fundamental step in phylogenetics, existing methods for this task consume computational resources for long processing time, they are not always feasible, and sometimes depend on preliminary assumptions which do not hold for sequence data. Moreover, although these methods are dedicated to revealing the processes that underlie the sequence data, they do not always produce the most accurate trees. Notably, phylogeny reconstruction consists of two related tasks, topology reconstruction and branch-length estimation. It was previously shown that in many cases the most complex model, GTR+I+G, leads to topologies that are as accurate as using existing model selection criteria, but overestimates branch lengths. Here, we present ModelTeller, a computational methodology for phylogenetic model selection, devised within the machine-learning framework, optimized to predict the most accurate nucleotide substitution model for branch-length estimation. We demonstrate that ModelTeller leads to more accurate branch-length inference than current model selection criteria on data sets simulated under realistic processes. ModelTeller relies on a readily implemented machine-learning model and thus the prediction according to features extracted from the sequence data results in a substantial decrease in running time compared with existing strategies. By harnessing the machine-learning framework, we distinguish between features that mostly contribute to branch-length optimization, concerning the extent of sequence divergence, and features that are related to estimates of the model parameters that are important for the selection made by current criteria.


The fruits of authorship.
Scientific paper authorship is an important academic achievement for all research professionals. Being designated as an author of a paper has academic, research, social and financial implications. Signing of a manuscript as an author does confer credit but also transfers responsibility. While authors get credit for the published work, they must accept the public responsibility that goes with it. Over the past few years, there has been a rising trend in authorship abuses. The prevalent culture of "publish or perish" appears to be responsible for this. In an endeavor to ensure honest practice, the International Committee of Medical Journal Editors (ICMJE), the Vancouver Group, developed the criteria for authorship and said that "all persons designated as authors should qualify for authorship and all those who qualify should be listed." However, authorship irregularities continue to exist and are a cause of concern. Budding authors should be enlightened about concurrent problems in authorship, during their formative years and encouraged toward fair practices in publications.


Neonatal Sleep Restriction Increases Nociceptive Sensitivity in Adolescent Mice.
Sleep loss in infants may have a negative effect on the functional and structural development of the nociceptive system. We tested the hypothesis that neonatal sleep restriction induces a long-term increase of pain-related behaviors in mice and that this hypersensitivity occurs due to changes in the neuronal activity of nociceptive pathways. We aim to investigate the effects of sleep loss in neonatal mice on pain behaviors of adolescent and adult mice in a sex-dependent manner. We also analyzed neuroanatomical and functional changes in pain pathways associated with behavioral changes. An experimental animal study. A basic sleep research laboratory at Universidade Federal de São Paulo in Brazil. Neonatal mice at postnatal day (PND) 12 were randomly assigned to either control (CTRL), maternal separation (MS), or sleep restriction (SR) groups. MS and SR were performed 2 hours a day for 10 days (PND 12 until PND 21). The gentle handling method was used to prevent sleep. At PND 21, PND 35, or PND 90, the mice were tested for pain-related behaviors. Their brains were harvested and immunohistochemically stained for c-Fos protein in the anterior cingulate cortex, primary somatosensory cortex, and periaqueductal gray (PAG). Neonatal SR significantly increased nociceptive sensitivity in the hot plate test in adolescent mice (-23.5% of pain threshold). This alteration in nociceptive response was accompanied by a decrease in c-Fos expression in PAG (-40% of c-Fos positive cells compared to the CTRL group). The hypersensitivity found in adolescent mice was not present in adult animals, and all mice showed a comparable nociceptive response. Even using a mild manipulation method, in which a minimal amount of handling was applied to maintain wakefulness, sleep deprivation was a stressful event evidenced by higher corticosterone levels. Repeated exposures to sleep loss during early life were able to induce changes in the nociceptive response associated with alterations in neural activity in descending control of pain. Brain maturation, hypersensitivity, neuronal activity, nociception, pain, periaqueductal gray, postnatal development, sleep, sleep deprivation.


Racial and ethnic differences in psychotropic medication use among community-dwelling persons with dementia in the United States.
Little is known about the patterns of psychotropic medication use in community-dwelling minority persons with dementia (PWD). The purpose of this study was to investigate racial/ethnic differences in psychotropic medication use across a diverse population of community-dwelling PWD and to examine the extent to which caregiver characteristics influence this use. Data were drawn from the baseline assessment of the Resources for Enhancing Alzheimer's Caregiver Health II trial. Generalized linear models were used to identify racial/ethnic differences in psychotropic medication use. Akaike Information Criterion (AIC) model selection was used to evaluate possible explanations for observed differences across racial/ethnic group. Differences in anxiolytic and antipsychotic medication use were observed across racial/ethnic groups; however, race/ethnicity alone was not sufficient to explain those differences. Perceptions of caregiving and caregiver socioeconomic status were important predictors of anxiolytic use while PWD characteristics, including cognitive impairment, functional impairment, problem behavior frequency, pain, relationship to the caregiver, sex, and age were important for antipsychotic use. Racial/ethnic differences in psychotropic medication use among community-dwelling PWD cannot be explained by race/ethnicity alone. The importance of caregiver characteristics in predicting anxiolytic medication use suggest that interventions aimed at caregivers may hold promise as an effective alternative to pharmacotherapy.


A 26K fragment of troponin T from rabbit skeletal muscle.
A 26K fragment of troponin T, which was produced by endogenous proteases in rabbit skeletal muscle, was isolated by SE-Sephadex column chromatography. This fragment sensitized both superprecipitation and ATPase of actomyosin to calcium ions, to the same extent as troponin T. There was no difference in affinity for tropomyosin between this fragment and troponin T as examined by affinity chromatography. Amino acid analysis showed that this fragment consisted of residues Ala-46-Lys-259 of troponin T. The N-terminal 45 residues of troponin T, therefore, are not essential for the physiological action of troponin T. It was also observed that Ca2+-activated neutral protease digested troponin T into the 26K fragment in the native thin filament, while the protease digested troponin T in a different way in the reconstituted thin filament.


[Optimal treatment of benign prostatic hyperplasia (BPH) with comorbid chronic prostatitis (category IIIA)].
The trial of efficacy of physical factors in combined treatment of BPH stage I patients with concomitant abacterial chronic prostatitis (category IIIA) enrolled 42 patients who were divided into two groups. Group 1 received combined treatment including complex physical factors (CAP-ELM-01). The efficacy of the treatment was judged by dynamics of clinical and device indices and severity of leading CP syndromes. It is shown that physical factors contributed to noticeable improvement in the parameters of prostatic secretion, uroflowmetry, size of the prostate, hemodynamics, clinical manifestations of chronic prostatitis.


White matter hypoperfusion and damage in dementia: post-mortem assessment.
Neuroimaging has revealed a range of white matter abnormalities that are common in dementia, some that predict cognitive decline. The abnormalities may result from structural diseases of the cerebral vasculature, such as arteriolosclerosis and amyloid angiopathy, but can also be caused by nonstructural vascular abnormalities (eg, of vascular contractility or permeability), neurovascular instability or extracranial cardiac or vascular disease. Conventional histopathological assessment of the white matter has tended to conflate morphological vascular abnormalities with changes that reflect altered interstitial fluid dynamics or white matter ischemic damage, even though the latter may be of extracranial or nonstructural etiology. However, histopathology is being supplemented by biochemical approaches, including the measurement of proteins involved in the molecular responses to brain ischemia, myelin proteins differentially susceptible to ischemic damage, vessel-associated proteins that allow rapid measurement of microvessel density, markers of blood-brain barrier dysfunction and axonal injury, and mediators of white matter damage. By combining neuroimaging with histopathology and biochemical analysis, we can provide reproducible, quantitative data on the severity of white matter damage, and information on its etiology and pathogenesis. Together these have the potential to inform and improve treatment, particularly in forms of dementia to which white matter hypoperfusion makes a significant contribution.


Effect of small and radical surgical injury on the level of different populations of circulating tumor cells in the blood of breast cancer patients.
Circulating tumor cells (CTCs) constitute a heterogeneous population. Some tumor cells are cancer stem cells (CSCs), while others are in the process of the epithelial-mesenchymal transition (EMT); however, most CTCs are neither stem cells nor in the EMT. This prospective study of 22 patients with nonspecific-type invasive carcinoma of the breast identified different populations of CTCs by flow cytometry in the blood of patients before biopsy, after biopsy and after surgical tumor removal without neoadjuvant chemotherapy. The results showed that minor surgical injury (biopsy) was accompanied by a significant increase in the blood levels of CTCs without signs of the EMT or stemness (Epcam+CD45-CD44-CD24-Ncadh-) and CTCs with signs of stemness and without signs of the EMT (Epcam+CD45-CD44+CD24-Ncadh-). Our results suggest that minor surgical injury to a tumor contributes to the release of CTCs into the bloodstream, including a population of stem cells.


Comparison of the effects of antenatal magnesium sulphate and ritodrine exposure on circulatory adaptation in preterm infants.
We examined the effects of maternal magnesium sulphate (MgSO4) and ritodrine treatments on the autonomic cardiovascular control in preterm neonates with respiratory distress syndrome during the first 2 days of life. Serial measurements of heart rate (HR), blood pressure (BP) and respirogram were performed during the first 2 days of life in 28 preterm infants below 33 weeks of gestation with antenatal exposure to MgSO4 (n = 13) or ritodrine (n = 15), and in 12 nonexposed preterm controls. Spectral analysis was used for the quantification of HR and BP variability. Although antenatal MgSO4 exposure had no effect on HR or the systolic, diastolic or mean BP, it was associated with significant decreased beat-to-beat changes in BP. In contrast, ritodrine exposure had no consistent effects on the autonomic cardiovascular control during the first 2 days of life. Our data suggest that maternal MgSO4 treatment decreases the neonatal high frequency changes in BP. This early vascular stabilizing effect of antenatal MgSO4 exposure may contribute to a lowered risk of cerebral vascular catastrophes, in the vulnerable areas of the brain, among the preterm infants with respiratory distress syndrome.


Problems in the necropsy diagnosis of alcoholic liver disease.
Problem areas in the necropsy diagnosis of alcoholic liver disease are reviewed, potential sources of confusion delineated, and diagnostic guidelines proposed. The entire spectrum of alcoholic liver disease, including alcoholic hepatitis, may be perfectly mimicked by severe obesity, diabetes, and perhexiline maleate toxicity. Focal fatty change in the liver introduces sampling errors in the assessment of steatosis. Nodular regenerative hyperplasia of the liver mimics a micronodular cirrhosis both clinically and macroscopically. Measurement of the liver iron concentration reliably differentiates between alcoholic liver disease with siderosis and idiopathic hemochromatosis. The evaluation of preexisting fibrosis or cirrhosis in cases of massive hepatic necrosis is aided by stains for elastic fibers. Alcohol abusers taking acetaminophen (paracetamol) in excessive, but not suicidal doses are at risk of developing fatal "late" acetaminophen hepatotoxicity. Fatal viral hepatitis may be overlooked in an alcoholic with preexisting liver disease.


The 21st-century landscape of adult fractures: cohort study of a complete adult regional population.
Recent reports on adult fracture epidemiology have focused mainly on the hip in the elderly, in whom increasing rates lately have changed to a decline. New reports of the preponderance of nonhip fractures in health expenditure call for a wider scope. We therefore examined current overall and site-specific fracture epidemiology in adults. We ascertained all fractures diagnosed in inpatient and outpatient care in all men and women aged 20 years or older in Skåne County, Sweden, from 1999 to 2010 (10 million person-years). For each fracture type, we estimated age-specific and sex-specific rates and evaluated potential time trends. We found 205,908 fractures yielding an overall fracture rate of 192 per 10,000 person-years. The age-standardized overall fracture rate increased by 1.2 per 10,000 and year (95% confidence interval, 0.8 to 1.5), but time trends were different for different fracture types, age strata, and for men and women. For example, in both women and men aged ≥50 years the rates of proximal humerus fracture increased (0.6 and 0.2 per 10,000 and year, respectively) while hip fracture rates declined (-1.0 and -0.3 per 10,000/year, respectively). Overall age-specific number of fractures increased with age in women but was stable in men. The increasing overall fracture rate is a major concern in the context of a growing and aging population. Effective and affordable preventive strategies and treatments should be an urgent priority to meet the challenges, especially in older women in whom most fractures occur. Comprehensive current detailed data, as provided in this study, may serve as reference for projections and for cost calculations of fracture care in other settings before results of similar examinations are available there.


Validity and Reliability of the Arabic Version of the Three-Factor Eating Questionnaire-R18.
The present study translated and validated an Arabic version of the Three-Factor Eating Questionnaire-R18 (TFEQ-R18), which assesses eating behaviour traits among Arabic speakers in the three domains: cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). Three bilingual experts first translated the English questionnaire into Arabic, and the questionnaire's comprehension was tested among 298 Arabic speakers. Confirmatory factor analysis (CFA) tested the model fit and flagged four items in the questionnaire with low consistency. These items were modified, and the revised Arabic version of TFEQ-R18 was validated in a population of 513 individuals. Validity was evaluated using CFA and Pearson's correlation coefficients, internal consistency using Cronbach's α, and the reproducibility of the questionnaire was confirmed with Bland-Altman analysis and T-test. The construct validity of the Arabic TFEQ-R18 was evaluated by comparing the response score in the population based on gender, BMI and age group. CFA confirmed that the model fit is good and strongly agrees with the collected data. Except for item 15 in the CR domain, all questions showed moderate to high correlation within their respective domains. The Cronbach's α for UE, EE, and CR domains recorded was 0.778, 0.784 and 0.588, respectively. Item 15 had the lowest consistency in the Arabic-TFEQ-R18, and Cronbach's α increased to 0.608 with its removal. There was no significant difference between the first and second attempts of the Arabic TFEQ-R18, indicating good test-retest reliability. Moreover, UE and EE were positively correlated to the BMI of the participants (r = 0.159, p = 0·000; r = 0.158, p = 0·000, respectively). The study concludes that the Arabic TFEQ is a valid and reliable tool for studying the three psychometric domains of UE, EE and CR among Arabic speakers.


Genomic characterization of respiratory syncytial virus genotypes circulating in the paediatric population of Sydney, NSW, Australia.
Respiratory syncytial virus (RSV), or human orthopneumovirus, is a major cause of acute lower respiratory infection (ALRI), particularly in young children, causing significant morbidity and mortality. We used pathogen genomics to characterize the population structure and genetic signatures of RSV isolates circulating in children in New South Wales between 2016 and 2018 and to understand the evolutionary dynamics of these strains in the context of publicly available RSV genomes from the region and globally. Whole-genome phylogenetic analysis demonstrated the co-circulation of a few major RSV clades in the paediatric population from Sydney. The whole-genome-based genotypes A23 (RSV-A ON1-like genotype) and B6 (RSV-B BA9-like genotype) were the predominant RSV-A and RSV-B genotypes circulating during the study period, respectively. These genotypes were characterized with high levels of diversity of predicted N- and O-linked glycosylation patterns in both the G and F glycoproteins. Interestingly, a novel 72-nucleotide triplication in the sequence that corresponds to the C-terminal region of the G gene was identified in four of the A23 genotype sequenced in this study. Consistently, the population dynamics analysis demonstrated a continuous increase in the effective population size of A23 and B6 genotypes globally. Further investigations including functional mapping of mutations and identifying the impact of sequence changes on virus fitness are highly required. This study highlights the potential impact of an integrated approach that uses WG-based phylogeny and studying selective pressure events in understanding the emergence and dissemination of RSV genotypes.


Vegetable fermentations brined with low salt for reclaiming food waste.
Fermentation of eight vegetables was studied as an alternative for reclamation of surplus volumes. Fermentation performance was predicted by comparing the amounts of acid that could be produced from the intrinsic sugar content with that buffered by the fresh vegetable matrices prior to reaching an inhibitory pH for fermentative microbes (3.30). Native fermentations were brined with 345.0 mM sodium chloride, 40.0 mM calcium chloride, 6.0 mM potassium sorbate, and vinegar to adjust the initial pH to 4.70. High-performance liquid chromatography analysis, pH, and carbon dioxide measurements and spiral plating on selective media were employed to monitor the progress of fermentations. The average colony counts for yeast and/or molds and Enterobacteriaceae declined to undetectable levels from 3.6 ± 1.5 log CFU/ml within 7 days of fermentation. The fermentation of sugars produced lactic, acetic, succinic, and/or malic acids, and ethanol. As predicted, the fermentation of vegetables with low sugar content, such as broccoli, green leaf lettuce, and green pea proceeded to completion. The fermentation of vegetables with a moderate sugar content, such as green bell pepper, red ripened tomato, and green bean were incomplete at pH 3.1 ± 0.2. The fermentation of high sugar vegetables including sweet potato and corn were expected and observed to be incomplete. It is concluded that the intrinsic sugar content and buffer capacity of surplus vegetables are relevant parameters in obtaining complete fermentations. PRACTICAL APPLICATION: Vegetables are the second most wasted commodity in the United States and a substantial constituent of the global food waste. Development of fermentation to reclaim surplus vegetables from farms, grocery stores, and farmer's markets offers opportunities to ameliorate economic losses and environmental impact and add value to waste. The research described here suggests that a fraction of vegetables could be fermented in cover brines while others, with high sugar content, need specialized handling. Evidently, optimization of vegetable fermentation with starter cultures and added buffers represent an opportunity to stimulate complete bioconversions useful for reclaiming surplus volumes.


The association of fasting blood glucose (FBG) and waist circumference in northern adults in Iran: a population based study.
The aim of this study was to evaluate the association between Fasting Blood Glucose (FBG) level and Waist Circumference (WC) in men and women among 25-65 years old people in the north of Iran. This was a cross-sectional and analytical research gender that carried out on the 1797 subjects (941 males and 856 females) between 25-65 years old using multistage cluster sampling technique. FBG was measured in the morning after a 12-hour fast and was determined by using laboratory kits (enzymatic methods) and spectrophotometry technique. Central obesity was defined based on World Health Organization criteria: waist circumference ≥102 cm and ≥88 cm in men and women, respectively. The SPSS.16 software was used for statistical analysis. As whole, the mean of FBG in women (98.3 ± 40.1 mg/dl) was higher than in men (94.6 ± 32.2 mg/dl). Also, the mean of WC in men 4.5 cm was lower than in women. In men, the mean of FBG statistically differs between normal and central obese subjects both in 35-45 year-age group (P = 0.001) and in 45-55 year-age group (P = 0.042). As whole, in men, the FBG level increased up 2.82 mg/dl in each 10 cm of WC with the highest rate in 35-45 year-age group. In totally, in women, the FBG level increased up 3.48 mg/dl in each 10 cm of WC and in 25-35 year-age group and it was higher than in other age groups. In men, the regression coefficients were constant with age increasing while in women it was decreased. Constant trend in men and decreasing trend in women with age was shown between FBG and WC. The cut-off point of WC for detecting of diabetes obtained 89 cm and 107 cm in men and women, respectively. The positive correlation was seen between WC and FBG level and it was declined with age in women. Cut-off point for detecting of diabetes in men was less than in women. WC is useable as a predictor of type 2 diabetes mellitus risk among adults in the north of Iran.


Unraveling the connection between calreticulin and myeloproliferative neoplasms via calcium signaling.
Mutations in the form of insertions and deletions (INDEL) in the calreticulin gene lead to essential thrombocythemia (ET) which is characterized by the formation of thrombosis. However, the connection between calreticulin INDEL and ET remains largely elusive. Through combined molecular dynamics simulation, clustered regularly interspaced short palindromic repeats (CRISPR) and calcium imaging studies on the wild type and mutated isoforms of calreticulin, the mechanism underlying the calreticulin INDEL induced ET was investigated at the molecular level. Our results demonstrate that mutations in exon-9 could lead to significant conformational variations of calreticulin structure and thereby reducing its interaction with calcium ions due to decreased electrostatic contributions. The consequence of mutations on calreticulin's structural integrity was revealed by identifying the key residues and their roles in calcium binding. Furthermore, mutations implemented by CRISPR-Cas9 in exon-9 showed diminished calcium signaling in HEK-293T cells, which agree well with our in-silico findings. The current study might help in understanding the variations of molecular interactions between calreticulin's exon-9 and calcium ions during physiological and pathological conditions. The results might also provide useful information for designing novel therapeutic approaches targeting ET.


Metachronous adrenal metastasis from operated contralateral renal cell carcinoma with adrenalectomy and iatrogenic Addison's disease.
Metachronous adrenal metastasis from contralateral renal cell carcinoma (RCC) surgery is an extremely rare condition. Iatrogenic Addison's disease occurring after metastasectomy (adrenalectomy) is an even rarer clinical entity. We present a case of a 68-year-old male with hematuria and left flank pain 9 years prior. The patient underwent left transperitoneal radical nephrectomy involving the ipsilateral adrenal glands due to a centrally-located, 75-mm in diameter solid mass lesion in the upper pole of the left kidney. The tumour lesion was confined within the renal capsule, and the histo-pathological examination revealed a Fuhrman nuclear grade II clear cell carcinoma. The patient underwent transperitoneal right adrenalectomy. The histopathological examination revealed metastasis of clear cell carcinoma. The patient was diagnosed with iatrogenic Addison's disease based on the measurement of serum cortisol levels and the adrenocorticotropic hormone (ACTH) stimulation test, after which glucocorticoid and mineralocorticoid replacement was initiated. The patient did not have local recurrence or new metastasis in the first year of the follow-up. The decision to perform ipsilateral adrenalectomy during radical nephrectomy constitutes a challenge, and the operating surgeon must consider all these rare factors.


Tailor-made development of fast Li ion conducting garnet-like solid electrolytes.
This paper reports a novel approach to designing advanced solid Li ion electrolytes for application in various solid state ionic devices, including Li ion secondary batteries, gas sensors, and electrochromic displays. The employed methodology involves a solid-solution reaction between the two best-known fast Li ion conductors in the garnet-family of compounds Li(6)BaLa(2)M(2)O(12) (M = Nb, Ta) and Li(7)La(3)Zr(2)O(12). Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), AC impedance, and (7)Li nuclear magnetic resonance (Li NMR) spectroscopy were employed to characterize phase formation, morphology, ionic conductivity, and Li ion coordination in Li(6.5)La(2.5)BaZrMO(12). PXRD shows for formation of a cubic garnet-like structure and AC impedance data is consistent with other known solid Li ion electrolytes. Li(6.5)La(2.5)BaZrTaO(12) exhibits a fast Li ion conductivity of about 6 x 10(-3) S cm(-1) at 100 degrees C, which is comparable to that of currently employed organic polymer electrolytes value at room temperature. The Nb analogue shows an order of magnitude lower ionic conductivity than that of the corresponding Ta member, which is consistent with the trend in garnet-type electrolytes reported in the literature. Samples sintered at 1100 degrees C shows the highest electrical conductivity compared to that of 900 degrees C. (7)Li MAS NMR shows a sharp single peak at 0 ppm with respect to LiCl, which may be attributed to fast migration of ions between various sites in the garnets, and also suggesting average distributions of Li ions at average octahedral coordination in Li(6.5)La(2.5)BaZrMO(12). The present work together with literature used to establish very important fundamental relationship of functional property-Li concentration-crystal structure-Li diffusion coefficient in the garnet family of Li ion electrolytes.


Tuning of Schottky Barrier Height at NiSi/Si Contact by Combining Dual Implantation of Boron and Aluminum and Microwave Annealing.
Dopant-segregated source/drain contacts in a p-channel Schottky-barrier metal-oxide semiconductor field-effect transistor (SB-MOSFET) require further hole Schottky barrier height (SBH) regulation toward sub-0.1 eV levels to improve their competitiveness with conventional field-effect transistors. Because of the solubility limits of dopants in silicon, the requirements for effective hole SBH reduction with dopant segregation cannot be satisfied using mono-implantation. In this study, we demonstrate a potential solution for further SBH tuning by implementing the dual implantation of boron (B) and aluminum (Al) in combination with microwave annealing (MWA). By using such a method, not only has the lowest hole SBH ever with 0.07 eV in NiSi/n-Si contacts been realized, but also the annealing duration of MWA was sharply reduced to 60 s. Moreover, we investigated the SBH tuning mechanisms of the dual-implanted diodes with microwave annealing, including the dopant segregation, activation effect, and dual-barrier tuning effect of Al. With the selection of appropriate implantation conditions, the dual implantation of B and Al combined with the MWA technique shows promise for the fabrication of future p-channel SB-MOSFETs with a lower thermal budget.


[Chemical components of Trachelospelmun jasminoides (Lindl.) Lem. var. heterophyllum Tsiang].
Five kind of crystal products were isolated from the methyl alcohol extract of Trachelospelmum jasminoides var. heterophyllum. By using chemical analysis and spectrogrophical identification, four of these five products were proved to be arctigenin-4'-beta-gentiobiosid,tracheloside and two kinds of optical isomer of beta-tracheloside. The last two were found in this genus for the first time.


BeO6 Trigonal Prism with Ultralong Be-O Bonds Observed in a Deep Ultraviolet Optical Crystal Li13BeBe6B9O27.
Beryllium (Be) has high ionization energy (9.32 eV) with the greatest degree of covalency in the group IIA elements, and BeO4 tetrahedra (and BeO3 triangles) with covalent character are generally presented in beryllates. An unprecedented BeO6 trigonal prism with ultralong Be-O bonds as well as a BeO4 common tetrahedron is discovered in a new deep ultraviolet crystal Li13BeBe6B9O27 (LBeBBO) with a ∞2[Be6B9O33] double-layer framework. The BeO6 unit and its bond character are verified by an isostructural crystal Li13(Mg0.45Be0.55)Be6B9O27, while the orbital theory and charge density difference further clarify the ionic character of the BeO6 unit. Phonon dispersion confirms the structural stability of LBeBBO.


First-line therapy in atypical hemolytic uremic syndrome: consideration on infants with a poor prognosis.
Atypical hemolytic uremic syndrome (aHUS) is a rare and heterogeneous disorder. The first line treatment of aHUS is plasma therapy, but in the past few years, the recommendations have changed greatly with the advent of eculizumab, a humanized monoclonal anti C5-antibody. Although recent recommendations suggest using it as a primary treatment for aHUS, important questions have arisen about the necessity of immediate use of eculizumab in all cases. We aimed to draw attention to a specific subgroup of aHUS patients with rapid disease progression and high mortality, in whom plasma therapy may not be feasible. We present three pediatric patients of acute complement-mediated HUS with a fatal outcome. Classical and alternative complement pathway activity, levels of complement factors C3, C4, H, B and I, as well as of anti-factor H autoantibody and of ADAMTS13 activity were determined. The coding regions of CFH, CFI, CD46, THBD, CFB and C3 genes were sequenced and the copy number of CFI, CD46, CFH and related genes were analyzed. We found severe activation and consumption of complement components in these patients, furthermore, in one patient we identified a previously not reported mutation in CFH (Ser722Stop), supporting the diagnosis of complement-mediated HUS. These patients were not responsive to the FFP therapy, and all cases had fatal outcome. Taking the heterogeneity and the variable prognosis of atypical HUS into account, we suggest that the immediate use of eculizumab should be considered as first-line therapy in certain small children with complement dysregulation.


Cyclodextrin-crosslinked poly(acrylic acid): Synthesis, physicochemical characterization and controlled release of diflunisal and fluconazole from hydrogels.
The aim of this work was to develop mucoadhesive hydrogels with variable drug delivery properties by crosslinking poly(acrylic acid) (PAA) with cyclodextrins (CDs). CD-PAA polymers with high CD content and good inter-batch reproducibility were synthesized by activating PAA with SOCl2, then reacting PAA chloride with CD in the presence of 4-dimethylaminopyridine at 50°C. Manipulation of the synthesis conditions affected the physicochemical character of the CD-PAA polymers and hydrogels in terms of CD content, the average number of ester bonds to an individual CD, viscosity, and the association and release of model drugs. Inclusion complexation of diflunisal (DIF) and fluconazole (FLZ) with CD-PAA hydrogels was assessed by (19)F NMR spectroscopy and association constants (Kas) for DIF were in the range 220-486M(-1) with βCD-PAA and 1327-6055M(-1) with hydroxypropyl-βCD-PAA. For FLZ the Ka range was 34-171M(-1) with hydroxypropyl-βCD-PAA. The hydrogels were found to release both drugs by means of Fickian diffusion as the predominant mechanism. A slight trend toward negative correlation was found between the Ka and Higuchi kH values for DIF. These results highlight the potential of CD-PAA hydrogels to control the release of model drugs through inclusion complexation.