Cerebellar hemangioblastoma and primary hyperparathyroidism.
The authors report the case of a 52-year-old woman presenting with cerebellar hemangioblastoma and primary hyperparathyroidism. It is the second reported case involving this new association. The relationship between these two tumors is discussed.


Extreme hyponatremia in patients with myelomatosis: an effect of cationic paraproteins.
Three patients with IgG myelomatosis and extreme hyponatremia are described. By isoelectric focusing of the M-component it is demonstrated that the subnormal sodium value is most likely explained by a cationic effect of the myeloma globulin.


Staged endovascular repair of bilateral internal iliac artery aneurysms.
Internal iliac artery (IIA) aneurysms present several challenges to the vascular surgeon: They are uncommon, and the often difficult repair is associated with relatively high morbidity/mortality. Bilateral internal iliac disease adds technical complications secondary to ischemic complications. In this case, a 76-year-old male with bilateral IIA aneurysms underwent staged endovascular coil embolization, resulting in exclusion of flow to the aneurysms and avoidance of ischemic postoperative complications. Angiography during the procedure verified complete bilateral IIA occlusion, which remained intact at 6-week and 1 year follow-up (computed tomography). This case illustrates successful repair of bilateral IIA using endovascular techniques.


Confirmation by LC-MS/MS of azaspiracids in shellfish from the Portuguese north-western coast.
The search for azaspiracids (AZAs) in shellfish on the Portuguese coast started in 2002, but the presence of these toxins could not be demonstrated until the summer of 2006. Analysis by liquid-chromatography-tandem mass spectrometry (LC-MS/MS) allowed the confirmation of AZA2 as a dominant compound, followed by AZA1, in blue mussel (Mytilus galloprovincialis), common cockle (Cerastoderma edule), clams (Venerupis senegalensis, Ruditapes decussatus), razor clam (Solen marginatus) and oyster (Crassostrea spp). Traces of AZA3 were found only in blue mussel. Total levels of AZA1-3 determined in the whole flesh by LC-MS/MS ranged from 1.6 to 6.1 microg/kg. The finding of low levels of AZAs since 2002 suggests a low risk level when compared with the highest risks posed by diarrhetic shellfish poisoning (DSP) and paralytic shellfish poisoning (PSP) toxins. However, the limited number of years studied might generate a misleading conclusion. The contamination with PSP is an example, as no contamination occurred for an extended period of time between 1996 and 2004, despite high levels having occurred outside this period. Thus, there appears overall a moderate likelihood of occurrence of AZAs in the range that may be relevant to consumers.


Follow-up of pre-term infants: is correction of the developmental quotient for prematurity helpful?
Developmental quotients, measured on the Griffiths' scales, of 114 preterm infants of less than 34 wk gestation are compared with abnormal neurological findings at 1 yr of cerebral palsy, dystonia, and motor delay. The developmental quotient (DQ) uncorrected for prematurity more readily distinguishes the abnormal infant than the corrected DQ. It is recommended that while developmental follow-up still uses scales originally standardised on older preterm and full-term infants the uncorrected developmental quotient is also used. Ideally normative data on the preterm infant should be compiled as a basis for assessing development in these infants.


DNA methylation and transcription in HERV (K, W, E) and LINE sequences remain unchanged upon foreign DNA insertions.
DNA methylation and transcriptional profiles were determined in the regulatory sequences of the human endogenous retroviral (HERV-K, -W, -E) and LINE-1.2 elements and were compared between non-transgenomic and plasmid-transgenomic cells. DNA methylation profiles in the HERV (K, W, E) and LINE sequences were determined by bisulfite genomic sequencing. The transcription of these genome segments was assessed by quantitative real-time PCR. In HERV-K, HERV-W and LINE-1.2 the levels of DNA methylation ranged between 75 and 98%, while in HERV-E they were around 60%. Nevertheless, the HERV and LINE-1.2 sequences were actively transcribed. No differences were found in comparisons of HERV and LINE-1.2 CpG methylation and transcription patterns between non-transgenomic and plasmid-transgenomic HCT116 cells. The insertion of a 5.6 kbp plasmid into the HCT116 genome had no effect on the HERV and LINE-1.2 methylation and transcription profiles, although other parts of the HCT116 genome had shown marked changes. These repetitive sequences are transcribed, probably because the large number of HERV and LINE-1.2 elements harbor copies with non- or hypo-methylated long terminal repeat sequences.


Adult osteochondritis dissecans and focussed ESWT: A successful treatment option.
Extracorporeal shockwave therapy (ESWT) has gained acceptance in the medical field and in the treatment of non-unions and delayed bone healing. ESWT has been used effectively for many years as a noninvasive surgical procedure. The idea of treating Osteochondritis dissecans of knee and talus arose in the middle of the 1990's. OCD is known as a pre-arthritic factor in the long-term and still there is no consistent treatment. In the literature there is still only a small number of publications but international societies for shockwave treatment are convinced that ESWT on OCD shows to be an effective and safe method in the treatment of OCD in the early stages. We want to summarize the actual data on the treatment of OCD by ESWT.


The transformation of Saperda calcarata (Coleoptera: Cerambycidae) into a cellulose digester through the inclusion of fungal enzymes in its diet.
The larvae of the aspen borer, Saperda calcarata, which feed on the inner bark and sapwood of living aspen stems, are unable to digest cellulose. However, they can be transformed into cellulose digesters by adding the active cellulase complex of the fungus, Penicillium funiculosum to their diet. S. calcarata larvae are preadapted to exploit the digestive potential of ingested microbial enzymes. We argue that ingested fungal enzymes may be responsible for cellulose digestion in many, perhaps most or even all, cellulose digesting cerambycid beetles.


Microwave endometrial ablation for menorrhagia in patients with systemic disorders.
To evaluate the effectiveness of microwave endometrial ablation (MEA) in the treatment of menorrhagia in patients with severe systemic disease or medical conditions. Forty-two menorrhagic women undergoing systemic disorders with failure of medical management were treated with MEA under local or general anesthesia, and were followed-up for 1 year. The women had a mean age of 39.4 years (range, 17-49). The procedure was successfully completed in all patients, and no intraoperative complications occurred. Two cases died of their primary severe medical diseases within 2 months of treatment but these cases were not associated with MEA. Among the remaining 40 patients, 24 (60.0%) had amenorrhea within 12 months. The duration of hospitalization and the amount of blood transfusion were significantly reduced after treatment, and the quality of life of these patients was improved significantly. MEA is a safe and effective treatment for the management of severe menorrhagia in patients undergoing systemic illness or severe medical conditions.


[Activation-dependent characteristics of the electroencephalogram during visual information processing: II Results of an automatic amplitude analysis based on momentary values of signal voltage (author's transl)].
EEG was recorded in 16 Ss. under conditions of a modified "Konzentrations-Leistung-Test" including four levels of performance (balanced change-over design), and histograms of the momentary values of the signal voltages (derivation F3/01) constructed for frequency bands 4...8 Hz, 8...13 Hz and 13...26 Hz. The type of performance affected significantly standard deviations and the excesses in all frequency bands (multivariate analysis of variance, F-Test). Similar to the results of an interval analysis (Activ. ner. sup. 18, 1976, p. 244), the differences in mean values indicated the preponderant relevance of perceptual factors (NEWMAN-KEULS-Test). Four characteristics showed a significant activation dependence: the standard deviations of the amplitude distributions in the frequency bands 4...8 Hz and 13...26 Hz, corresponding to the root-mean--square values of the signal voltages, as well as the excesses in the frequency bands 8...13 Hz and 13...26 Hz. Only and amplitude of the theta waves were influenced notably by mental arithmetics, significantly though only when this was done under conditions of time stress.


Exendin-4 promotes proliferation of adipose-derived stem cells through ERK and JNK signaling pathways.
Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of exendin-4 (Ex-4), a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD90 and CD29 but negative for CD31, CD34, and CD45. Ex-4 (0-50 nM) treatment increased ADSC proliferation in a dose-dependent manner but had no effects on stem cell markers of ADSCs. Moreover, we found that Ex-4 treatment elevated the phosphorylation levels of the JNK and ERK signaling pathways. Furthermore, utilization of Ex-4 also promoted cyclin D1 and cyclin E protein expression, which was accompanied by more Edu(+) cells and a higher percentage of cells in the S-phase of the cell cycle after Ex-4 treatment. In parallel, the application of inhibitors SP600125 and PD98059, inhibitors of the JNK and ERK signaling pathways, respectively, not only reversed such effects of Ex-4 on JNK and ERK but also resulted in lower percentages of S-phase cells and fewer numbers of Edu(+) cells. In summary, Ex-4 has no effects on stem cell markers in ADSCs but promotes ADSC growth via JNK and ERK signaling pathways.


Left stellate ganglion block, a rescue treatment for ventricular arrhythmia refractory to radiofrequency catheter ablation: A care-compliant case report.
Stellate Ganglion Block (SGB) provides a blockade of sympathetic signals from the sympathetic chain and appears to be a promising method of controlling refractory ventricular arrhythmias, but there are scanty data in the literature. Herein, we describe a 59-year-old male patient with a history of non-ischemic cardiomyopathy and suffering from frequent VT episodes, who received ICD implantation and regular amiodarone medication control. Monomorphic VT refractory to standard medication control and focal extensive catheter ablation. Left Stellate Ganglion Block (LSGB) was performed under ultrasound-assisted injection at the C6 level using a 10 ml solution of 0.4% lidocaine and 0.5% bupivacaine. In our case, refractory VT subsided and sinus rhythm was retained immediately after LSGB. There were no VT episodes for at least 3 hours during the inter-hospital transfer, which did not involve any specific complications. LSGB may provide effective VT control and play an important role in rescue and bridge therapy before catheter ablation.


PAX7 is a required target for microRNA-206-induced differentiation of fusion-negative rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. RMS can be parsed based on clinical outcome into two subtypes, fusion-positive RMS (FP-RMS) or fusion-negative RMS (FN-RMS) based on the presence or absence of either PAX3-FOXO1 or PAX7-FOXO1 gene fusions. In both RMS subtypes, tumor cells show histology and a gene expression pattern resembling that of developmentally arrested skeletal muscle. Differentiation therapy is an attractive approach to embryonal tumors of childhood including RMS; however, agents to drive RMS differentiation have not entered the clinic and their mechanisms remain unclear. MicroRNA-206 (miR-206) expression increases through normal muscle development and has decreased levels in RMS compared with normal skeletal muscle. Increasing miR-206 expression drives differentiation of RMS, but the target genes responsible for the relief of the development arrest are largely unknown. Using a combinatorial approach with gene and proteomic profiling coupled with genetic rescue, we identified key miR-206 targets responsible for the FN-RMS differentiation blockade, PAX7, PAX3, NOTCH3, and CCND2. Specifically, we determined that PAX7 downregulation is necessary for miR-206-induced cell cycle exit and myogenic differentiation in FN-RMS but not in FP-RMS. Gene knockdown of targets necessary for miR-206-induced differentiation alone or in combination was not sufficient to phenocopy the differentiation phenotype from miR-206, thus illustrating that miR-206 replacement offers the ability to modulate a complex network of genes responsible for the developmental arrest in FN-RMS. Genetic deletion of miR-206 in a mouse model of FN-RMS accelerated and exacerbated tumor development, indicating that both in vitro and in vivo miR-206 acts as a tumor suppressor in FN-RMS at least partially through downregulation of PAX7. Collectively, our results illustrate that miR-206 relieves the differentiation arrest in FN-RMS and suggests that miR-206 replacement could be a potential therapeutic differentiation strategy.


Anthropometric measurements by ethnicity in Colombia, 1965-1990.
We analyzed the evolution of height in Colombia of cohorts born in the period 1965-1990 by ethnic groups. We found that Afro-Colombian men and women were the tallest: 6cm taller than indigenous people and 2cm taller than the rest of the population. We also found that the height gap between Afro-Colombians and others decreased during the period under study by 0.7cm for both men and women. While improvements were noticeable among the Afro-Colombians and those who chose not to be classified by ethnicity, in the case of the indigenous population only female cohorts registered an average-height increase of 1.5cm. Moreover, we found that indigenous Colombians were more likely than other ethnic groups to experience an increase in biological well-being as a consequence of an improvement in their socio-economic status, thereby reducing the average-stature gap between them and the rest of the population by 2.1 and 3.6cm for men and women, respectively.


New IS10 transposition vectors based on a gram-positive replication origin.
We describe below a set of plasmid-based vehicles which can be used for delivery of IS10-derived transposons into Gram- bacteria. These vehicles replicate via a Gram+ plasmid origin that is inactive in Escherichia coli; they are easily maintained in Bacillus subtilis. Transposons are introduced by electroporation or transformation with the plasmid, and as in previous delivery systems, transpositions are selected with the appropriate antibiotic. This system should be particularly useful in situations where the standard delivery vehicles, based on bacteriophage lambda, are inappropriate. The system described incorporates a number of useful features: a variety of antibiotic markers (Er, Cm, Km or Tc), a polylinker containing restriction sites for rare-cutting endonucleases to facilitate physical mapping of chromosomal insertions, a mutant transposase that confers a relaxation in insertion specificity and positioning of the transposase-encoding gene outside of the transposing segment to ensure the stability of insertions once isolated.


Injectable and photocurable CAR-T cell formulation enhances the anti-tumor activity to melanoma in mice.
The chimeric antigen receptor-T cells (CAR-T) therapy, as a novel personalized immunotherapy, has shown prominent clinical efficacy in the treatment of B-cell malignancies. However, the progress in solid tumors was hindered by multiple elements in the tumor immunosuppressive microenvironment. In this study, an injectable and photocurable Gelatin Methacryloyl (GelMA) hydrogel was applied to be a depot of CAR-T cells, thus forming an injectable CAR-T Gelatin Methacryloyl hydrogels Delivery (i-GMD) system. According to our results, CAR-T cells in this system could be normally amplified, sustained released, and play an anti-tumor role in vitro. When compared with local or intravenously injection of CAR-T solution, injection of i-GMD matrix around tumor demonstrated enhanced anti-tumor effect and markedly extended survival of mice. Our research outcomes indicated that this therapeutic strategy might hopefully provide a treatment for patients with unresectable tumors.


Hypophysectomy-induced inhibition of augmented acetylcholine responses of the rat bowel following adrenalectomy and/or whole body irradiation.
Functional changes in the intestinal responsiveness to a fixed dose of acetylcholine were studied in muscle strips removed from young adult male rats previously exposed to whole body gamma radiation. In the irradiated rat the responsiveness to a fixed dose of acetylcholine was found to be augmented in the small intestine but not in the colon. Similar motor patterns for the small intestine were found when muscle strips from adrenalectomized rats were studied. Preradiation adrenalectomy further exaggerated the post-radiation sensitivity of the rat small intestine to acetylcholine. Hypophysectomy prior to either adrenalectomy and/or whole body radiation was associated with an absence of augmented small intestinal motor activity following administration of acetylcholine. The response of the large bowel to acetylcholine, however, was not modified by adrenalectomy and/or hypophysectomy. These observations suggest an endocrine component to the acute 3--5 day intestinal radiation syndrome.


Technical note: Orbitozygomatic craniotomy using an ultrasonic osteotome for precise osteotomies.
The orbitozygomatic craniotomy is a fundamental procedure in neurosurgery, allowing access to orbital and skull base pathology. Determine the feasibility of using an ultrasonic osteotome to safely perform orbitozygomatic osteotomies in patients with intracranial pathology. The medical records of patients undergoing orbitozygomatic craniotomy using an ultrasonic osteotome (Aesculap BoneScalpel™) for tumor resection at Johns Hopkins Hospital between November 2009 and March 2013 were retrospectively reviewed. Six patients underwent orbitozygomatic craniotomy for tumor resection using an ultrasonic osteotome at the Johns Hopkins Hospital during the study period. All patients were female and the average age was 53.2 years. Patients were followed for an average of 375 days. There were two cases of transient diplopia. There were no cases of periorbital violation, orbital injury, enophthalmos, or orbital hematoma. Post-operative imaging showed the cuts were well opposed and no cosmetic issues were encountered. Use of an ultrasonic osteotome allows for precise cuts under direct visualization with minimal risk to critical adjacent structures in our cohort of patients undergoing a two-piece orbitozygomatic craniotomy. This appears to be a safe instrument for osteotomy creation in skull base approaches.


Cognitive set influences on Witkin's Rod-and-Frame Test.
Witkin's field-dependence theory is embroiled in conflict as research shows its primary assessment method, the Rod-and-frame Test, is influenced by situational events. This study explored the impact of an additional situational variable, locus of problem-solving data search, a cognitive set modified from Rotter's (1966) work. Two experimental groups of hospitalized alcoholics received standard Witkin instructions plus instructions emphasizing either an internal or external search for problem-solving cues. A control group received only Witkin's instructions. Aanlysis of variance showed the special instructions affected rod-and-frame scores in the predicted directions. The results were interpreted as indicating a need for a multi-factor approach to analyzing the complex relationships of the Rod-and-frame Test.


Chryseobacterium meningosepticum keratitis.
To describe a case of a corneal ulcer caused by Chryseobacterium meningosepticum in an eye without significant comorbidities. Interventional case report. Retrospective case review. A 48-year-old man presented with a corneal ulcer in his right eye and was treated with ofloxacin and fortified bacitracin ophthalmic solution. Cultures grew C. meningosepticum, and the infection resolved. Two previous case reports in the literature have described ocular infections with this bacterium, both in postoperative patients with significant ocular comorbidities. This is the first report of ocular infection with C. meningosepticum in an eye with no significant comorbidities.


Detection of intrapericardial hematoma after open heart surgery: the roles of echocardiography and computed tomography.
Two patients who had right atrial compression caused by intrapericardial hematomas after coronary artery bypass grafting and aortic valve replacement are described. During the course of postoperative evaluation, each patient underwent an echocardiographic examination followed by computed tomography of the chest. Two-dimensional echocardiography visualized the hematomas in both cases. Computed tomography played a useful adjunctive role by further clarifying their nature, location and extent.


Labor risk factors for fetal heart rate abnormality after combined spinal-epidural analgesia.
To explore the association between obstetric factors or outcomes and fetal heart rate (FHR) abnormalities after combined spinal-epidural analgesia (CSEA). Women with singleton term deliveries who received CSEA at our institution between January 1 and December 31, 2017, were analyzed using medical records. We performed a logistic regression analysis to compare factors and outcomes between cases with and without new FHR abnormalities within 1 h after CSEA. Of the 393 women, 163 showed the new occurrence of FHR abnormality after CSEA. Rupture of the membrane (odds ratio [OR] 2.49; 95% confidence interval [CI] 1.52-4.09; P < 0.01) and dilatation of the cervix (OR 1.24; 95% CI 1.07-1.44; P < 0.01) were significantly associated with FHR abnormalities. There were significant differences in FHR abnormality rates between women with cervical dilatation of 2 cm or less and 3 cm or more (OR 2.20; 95% CI 1.01-4.81; P = 0.047) and 6 cm or less and 7 cm or more (OR 2.46; 95% CI 1.01-6.01; P = 0.048). FHR abnormalities were not significantly associated with cesarean delivery during labor, instrumental delivery, APGAR score below 7 at 1 or 5 min, or umbilical arterial blood gas pH less than 7.2. Rupture of the membrane and an advanced dilated cervix were risk factors for FHR abnormality when CSEA was initiated.


A review of the findings on computed cranial tomography following intravenous contrast media.
The diagnostic contribution of contrast enhancement by intravenous injection of meglumine diatrizoate was assessed in 121 patients who received both plain and contrast enhanced cranial CT scans. The use of contrast enhancement was found to provide both an increased sensitivity in detection of lesions and some improvement in pathological differentiation of lesions. The use of contrast enhancement in addition to plain CT scans increases the reliability of CT scans in excluding such conditions as neoplasms, abscesses, and vascular malformations. Because the use of contrast medium is associated with morbidity (and significantly extends the length of the total study), the decision to employ contrast enhancement must be based upon a careful evaluation of the clinical, other radiological, and plain CT findings in the individual patient.


Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt.
Berberine acted as a natural medicine with multiple pharmacological activities. In the present study, we examined the effect of berberine against cerebral ischemia damage from cell cycle arrest and cell survival. Oxygen-glucose deprivation of PC12 cells and primary neurons, and carotid artery ligation in mice were used as in vitro and in vivo cerebral ischemia models. We found that the effect of berberine on cell cycle arrest during ischemia was mediated by decreased p53 and cyclin D1, increased phosphorylation of Bad (higher expression of p-Bad and higher ratio of p-Bad to Bad) and decreased cleavage of caspase 3. Meanwhile, berberine activated the PI3K/Akt pathway during the reperfusion, especially the phosphor-activation of Akt, to promote the cell survival. The neural protective effect of berberine was remained in the presence of inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (MEK), but was suppressed by the inhibitors of PI3K and Akt. We demonstrated that berberine induced cell cycle arrest and cell survival to resist cerebral ischemia injury.


AMPK promotes osteogenesis and inhibits adipogenesis through AMPK-Gfi1-OPN axis.
Several metabolic, genetic and oncogenic bone diseases share the common pathological phenotype of defective bone marrow stromal cell (BMSC) differentiation. Many reports in bone science in the past several years have suggested that the skeleton also has an endocrine role. The role of AMP-activated protein kinase (AMPK) as an energy metabolism sensor and how it regulates BMSC differentiation is largely unknown. In the current study, we used AMPK agonists to activate AMPK in MC3T3-E1 cells to investigate the functional roles of AMPK in osteogenesis. However, metformin and AICAR failed to activate AMPK consistently. Therefore, we established MC3T3-E1 and 3T3-L1 cell models of AMPK α subunit overexpression through lentivirus vector, in which AMPK was overactivated. AMPK hyperactivation stimulated MC3T3-E1 cell osteogenesis and inhibited 3T3-L1 cell adipogenesis. Osteopontin (OPN) mediated AMPK regulation of osteogenesis and adipogenesis. Furthermore, we provided evidence that the transcriptional repressor growth factor independence-1 (Gfi1) was downregulated and disassociated from the OPN promoter in response to AMPK activation, resulting in the upregulation of OPN. Overexpression of wild-type and dominant-negative Gfi1 modulated MC3T3-E1 osteogenesis and 3T3-L1 adipogenesis. Further evidence suggested that AMPK enhanced ectopic bone formation of MC3T3-E1 cells through the AMPK-Gfi1-OPN axis. In conclusion, AMPK was sufficient to stimulate osteogenesis of MC3T3-E1 cells and inhibit adipogenesis of 3T3-L1 cells through the AMPK-Gfi1-OPN axis. These findings helped elucidate the molecular mechanisms underlying AMPK regulation of osteogenesis and adipogenesis.


Competition for sites of attachment to hosts in three parapatric species of reptile tick.
Competition for sites of attachment to hosts by three species of reptile tick, Aponomma hydrosauri, Amblyomma albolimbatum and Amb. limbatum was investigated as a possible cause for the parapatric distributions found in these species throughout southern Australia. Two localities were chosen for detailed study; a boundary between Ap. hydrosauri and Amb. limbatum near Mt. Mary in the mid-north of South Australia and a boundary between Ap. hydrosauri and Amb. albolimbatum near Arno Bay on the Eyre Peninsula of South Australia. Comparisons of sites of attachment to hosts were made between hosts infested by one species of tick and hosts infested by two species of tick. At Mt. Mary, Ap. hydrosauri and Amb. limbatum adults attach more commonly in the ears and on the midback of their hosts, however, no evidence was found to suggest that competition between the species occurred for these sites. At Arno Bay, Amb. albolimbatum adults had similar sites of attachment to hosts as the other two species, however, significantly more of this species attach in the ears of their hosts. There is no difference in sites of attachment to hosts of Ap. hydrosauri females at Arno Bay and Mt. Mary. Ap. hydrosauri males at Arno Bay, however, show a shift in sites of attachment to hosts away from those sites occupied by Amb. albolimbatum males and females. This shift occurs only in cases where Amb. albolimbatum did not infest the same host. Although the shift in male Ap. hydrosauri sites of attachment to hosts can be explained in terms of past competition, there is no evidence to suggest that such competition in the past, or competition at present, maintains the parapatric boundaries found in these species of thick.


Nonopioidergic mechanism mediating morphine-induced antianalgesia in the mouse spinal cord.
Intrathecal (i.t.) pretreatment with a low dose (0.3 nmol) of morphine causes an attenuation of i.t. morphine-produced analgesia; the phenomenon has been defined as morphine-induced antianalgesia. The opioid-produced analgesia was measured with the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with low dose (0.3 nmol) of morphine time dependently attenuated i.t. morphine-produced (3.0 nmol) TF inhibition and reached a maximal effect at 45 min. Intrathecal pretreatment with morphine (0.009-0.3 nmol) for 45 min also dose dependently attenuated morphine-produced TF inhibition. The i.t. morphine-induced antianalgesia was dose dependently blocked by the nonselective mu-opioid receptor antagonist (-)-naloxone and by its nonopioid enantiomer (+)-naloxone, but not by endomorphin-2-sensitive mu-opioid receptor antagonist 3-methoxynaltrexone. Blockade of delta-opioid receptors, kappa-opioid receptors, and N-methyl-D-aspartate (NMDA) receptors by i.t. pretreatment with naltrindole, nor-binaltorphimine, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), respectively, did not affect the i.t. morphine-induced antianalgesia. Intrathecal pretreatment with antiserum against dynorphin A(1-17), [Leu]-enkephalin, [Met]-enkephalin, beta-endorphin, cholecystokinin, or substance P also did not affect the i.t. morphine-induced antianalgesia. The i.t. morphine pretreatment also attenuated the TF inhibition produced by opioid muagonist [D-Ala2, N-Me-Phe4,Gly-ol5]-enkephalin, delta-agonist deltorphin II, and kappa-agonist U50,488H. It is concluded that low doses (0.009-0.3 nmol) of morphine given i.t. activate an antianalgesic system to attenuate opioid mu-, delta-, and kappa-agonist-produced analgesia. The morphine-induced antianalgesia is not mediated by the stimulation of opioid mu-, delta-, or kappa-receptors or NMDA receptors. Neuropeptides such as dynorphin A(1-17), [Leu]-enkephalin, [Met]-enkephalin, beta-endorphin, cholecystokinin, and substance P are not involved in this low-dose morphine-induced antianalgesia.


High-density EEG power topography and connectivity during confusional arousal.
Confusional arousal is the milder expression of a family of disorders known as Disorders of Arousal (DOA) from non-REM sleep. These disorders are characterized by recurrent abnormal behaviors that occur in a state of reduced awareness for the external environment. Despite frequent amnesia for the nocturnal events, when actively probed, patients are able to report vivid hallucinatory/dream-like mental imagery. Traditional (low-density) scalp and stereo-electroencephalographic (EEG) recordings previously showed a pathological admixture of slow oscillations typical of NREM sleep and wake-like fast-mixed frequencies during these phenomena. However, our knowledge about the specific neural EEG dynamics over the entire brain is limited. We collected 2 consecutive in-laboratory sleep recordings using high-density (hd)-EEG (256 vertex-referenced geodesic system) coupled with standard video-polysomnography (v-PSG) from a 12-year-old drug-naïve and otherwise healthy child with a long-lasting history of sleepwalking. Source power topography and functional connectivity were computed during 20 selected confusional arousal episodes (from -6 to +18 sec after motor onset), and during baseline slow wave sleep preceding each episode (from - 3 to -2 min before onset). We found a widespread increase in slow wave activity (SWA) theta, alpha, beta, gamma power, associated with a parallel decrease in the sigma range during behavioral episodes compared to baseline sleep. Bilateral Broadman area 7 and right Broadman areas 39 and 40 were relatively spared by the massive increase in SWA power. Functional SWA connectivity analysis revealed a drastic increase in the number and complexity of connections from baseline sleep to full-blown episodes, that mainly involved an increased out-flow from bilateral fronto-medial prefrontal cortex and left temporal lobe to other cortical regions. These effects could be appreciated in the 6 sec window preceding behavioral onset. Overall, our results support the idea that DOA are the expression of peculiar brain states, compatible with a partial re-emergence of consciousness.


Real-world retrospective cohort study ARCTIC shows burden of comorbidities in Swedish COPD versus non-COPD patients.
This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014. These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population. A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population. A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs. 30.7%). Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients. Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001). The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.


High doses of soman protect against organophosphorus-induced delayed polyneuropathy but tabun does not.
Organophosphorus-induced delayed polyneuropathy (OPIDP) is thought to result from organophosphorylation of neuropathy target esterase (NTE; formerly known as neurotoxic esterase), followed by an "aging" of the phosphorylated NTE. Protection against OPIDP should thus be achieved by production of an inhibited but "nonaging" NTE. Inhibited NTE produced in vitro by interaction with any of the four resolved isomers of soman aged negligibly (M. K. Johnson, D. J. Read, and H. P. Benschop, 1985a, Biochem. Pharmacol., 34, 1945-1951). Therefore both unresolved soman and the most inhibitory isomer (C(-)P(+)) were tested in adult hens for effects on NTE and for ability to produce OPIDP. With improved prophylaxis and therapy of acute intoxication, birds survived greater than 100 X LD50 of unresolved soman and did not develop OPIDP. One day after dosing, about half of brain and spinal cord NTE was in an unmodified (unaged) inhibited form; at this time eight survivors were challenged with a neuropathic dose of diisopropyl phosphorofluoridate (DFP). No neuropathy developed in four out of eight birds and mild to moderate signs were seen in the other four. Nine challenge control birds receiving DFP after solvent all developed severe neuropathy. Partial protection was seen in three out of three birds dosed prior to DFP challenge with sufficient C(-)P(+) isomer of soman (1.2 mg/kg sc) to convert about half of the spinal cord NTE to unaged inhibited form. Protection was not related to cholinergic shock. Two birds which survived out of eight pretreated with tabun (12 mg/kg sc) had about as much NTE inhibited as after soman administration but it was all in the modified (aged) inhibited form; these birds were not protected against DFP-induced neuropathy. A limited histopathologic examination showed that typical neurodegenerative lesions were seen only in birds with clear clinical neuropathy.


Internal hernia as a complication of laparoscopic nissen fundoplication.
A rare case of strangulated small bowel through a defect in the falciform ligament is presented to emphasize the possibility of complication after the creation of a window in the falciform ligament during laparoscopic surgery.


Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice.
Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)-nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis.


Corrigendum to "Genetic variability and traits association in maize (Zea mays L.) varieties for growth and yield traits".
[This corrects the article DOI: 10.1016/j.heliyon.2021.e07939.].


A four-year longitudinal evaluation study of nursing image, self-esteem, and profession perception among nursing students.
This study aimed to investigate nursing students' nursing image, self-esteem, and profession perception over their 4 years of study. This longitudinal study was conducted during 2016 and 2020 education terms. This study was conducted with the same group of students in their first year and fourth year on the nursing faculty in Turkey. Scale for the Image of the Nursing Profession, Rosenberg Self-Esteem Inventory, and Perception of Nursing Profession Scale were used to collect research data. Nursing education process have a significant positive effect on the perception of the profession and a negative effect on nursing image and self-esteem. Targeted interventions should cultivate nursing image, promote self-esteem, and enrich the nursing curriculum to improve nursing students' profession perception.


Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes.
The immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival. ALC values were collected from patient records ≥ 2 years before, during or after primary treatment for high-grade serous ovarian cancer (HGSC). Lymphocyte subsets were assessed in peripheral blood by flow cytometry. CD8+ and CD20+ TIL were assessed by immunohistochemistry. Overall, patients had normal ALC values two or more years prior to diagnosis of HGSC. These values were not predictive of disease severity or survival upon subsequent development of HGSC. Rather, ALC declined upon development of HGSC in proportion to disease burden. This decline involved all lymphocyte subsets. ALC increased following surgery, remained stable during chemotherapy, but rarely recovered to pre-diagnostic levels. ALC values recorded at diagnosis did not correlate with CD8+ or CD20+ TIL but were associated with progression-free survival. Patients with high intrinsic ALC values show no clinical or survival advantage upon subsequent development of HGSC. ALC values at diagnosis are prognostic due to an association with disease burden rather than TIL. Therapeutic enhancement of ALC may be necessary but not sufficient to improve survival in HGSC.


[Expression and Significance of ACIN1 mRNA in Platelets of Lung Cancer].
During the occurring and developing of tumor, tumor-educated platelets mRNA profiles were altered. Since platelets are anuclear, the level of mRNAs is probably post-transcriptional regulated by the splicing maturation of pre-mRNA and alternative splicing. Apoptotic chromatin condensation inducer 1 (ACIN1) has been shown to be a component of a splicing-dependent multiprotein exon junction complex (EJC) and was involved in mRNA metabolism associated with splicing. This study analyzed the expression of ACIN1 mRNA in platelets, and explored its potential as a biomarker of lung cancer. 156 patients with lung cancer and 58 healthy controls in Shandong Cancer Hospital were collected. We isolated platelet pellets by low-speed centrifugation and extracted total RNA. The expression of ACIN1 mRNA in platelets was detected by RT-PCR, the results were analyzed statistically. And the relationship between expression of ACIN1 mRNA and clinical factors were also analyzed. The expression level of ACIN1 mRNA in platelets of patients with lung cancer was significantly higher than that in platelets of healthy controls (P=0.015). The ROC curve showed that the area under the curve of ACIN1 mRNA for detecting lung cancer were 0.608. The expression of ACIN1 mRNA in platelets of lung cancer has no significant relationship with age, gender, pathological type and metastasis or not (P>0.05). ACIN1 mRNA was highly expressed in platelets of lung cancer patients, and the detection of its expression level might have potential clinical value for the diagnosis of lung cancer.


Effect of chronic administration of magnesium supplement (magnesium glycinate) on male albino wistar rats' intestinal (Ileum) motility, body weight changes, food and water intake.
Recent researches suggests magnesium as an adjuvant medication for COVID 19 patients. Magnesium relaxes skeletal muscles, an effect when prolonged in intestinal smooth muscles can cause severe discomfort such as bloating, vomiting, constipation and nausea. The objectives of this study was to ascertain if magnesium will cause relaxation of the intestinal (ileum) smooth muscles as it does in skeletal muscles. Also, this research seeks to find out the receptor pathway through which magnesium will alter motility in the gut using acetylcholine, atropine and propranolol. Ten male albino wistar rats (100-150 g) were randomly assigned into two groups (control and magnesium treated) (n = 5). Animals were acclimatized for two weeks before treatment which lasted for 6 weeks. Magnesium treated animals received oral magnesium glycinate (1600 mg/70 kg) daily while control group receive normal saline of equal volume. All animals had free access to food and water ad libitum. Results were analyzed at statistical level of P < 0.05. Body weight changes, food and water intake were not statistically significant. Basal contractions of ileum in magnesium treated group were significantly lower compared to control group. Propranolol significantly increased the percentage relaxation in magnesium treated group compared to the control. Atropine significantly decrease the percentage relaxation in magnesium treated group compared to the control. Higher doses of acetylcholine (10-5 and 10-4) increased the contractions in magnesium treated group. Conclusively, magnesium decreases motility of the intestine through beta adrenergic receptor pathway. Intake of magnesium for long period should be closely monitored to avoid the discomforting symptoms earlier stated.


Anomaly of the supraclavicular nerve: case report and review of the literature.
We report a male cadaver found to have his right intermediate branch of the supraclavicular nerve piercing the clavicle. No other anomalies were found in this specimen. Following a review of the literature, it appears that symptoms related to this finding are rare but do occur most commonly involving the intermediate branch of the supraclavicular nerve. Symptoms may be alleviated with surgical decompression of the entrapped nerve. Although rare, the clinician should include entrapment of the supraclavicular nerve within the clavicle in their differential diagnosis of shoulder pain.


Induction of the mesenchymal to epithelial transition by demethylation- activated microRNA-200c is involved in the anti-migration/invasion effects of arsenic trioxide on human breast cancer cells.
Breast cancer is a major health problem worldwide. Current standard practices for treatment of breast cancer are less than satisfactory because of high rates of metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and causes apoptosis, has been used as an anti-tumor agent. Little is known, however, regarding its anti-metastatic effects. The microRNA-200c (miR-200c), which is frequently lowly expressed in triple negative breast cancers (TNBCs), inhibits metastasis by inducing the mesenchymal to epithelial transition (MET). Here, we report that As(2)O(3) attenuates the migratory and invasive capacities of breast cancer cells, MDA-MB-231 and BT-549. Notably, As(2)O(3) induces an MET in vitro and in vivo, as determined by the increased expression of the epithelial marker, E-cadherin and decreased expressions of mesenchymal markers, N-cadherin and vimentin. Moreover, As(2)O(3) up-regulates the expression of miR-200c through demethylation. Over-expression of miR-200c enhances the expression of E-cadherin and decreases the expressions of N-cadherin and vimentin. Further, in MDA-MB-231 cells exposed to As(2)O(3), knockdown of miR-200c blocks the As(2)O(3) -induced MET. Finally, in MDA-MB-231 and BT-549 cells exposed to As(2)O(3), knockdown of miR-200c decreases the As(2)O(3) -induced inhibition of the migratory and invasive capacities. By identifying a mechanism whereby As(2)O(3) regulates miR-200c and MET, the results establish the anti-migration/invasion potential of arsenic trioxide.


Using the fluorescence decay of 2-aminopurine to investigate conformational change in the recognition sequence of the EcoRV DNA-(adenine-N6)-methyltransferase on enzyme binding.
The EcoRV DNA methyltransferase methylates the first adenine in the GATATC recognition sequence. It is presumed that methylation proceeds by a nucleotide flipping mechanism but no crystal structure is available to confirm this. A popular solution-phase assay for nucleotide flipping employs the fluorescent adenine analogue, 2-aminopurine (2AP), substituted at the methylation target site; a substantial increase in fluorescence intensity on enzyme binding indicates flipping. However, this appeared to fail for M.EcoRV, since 2AP substituted for the non-target adenine in the recognition sequence showed a much greater intensity increase than 2AP at the target site. This anomaly is resolved by recording the fluorescence decay of 2AP which shows that the target 2AP is indeed flipped by the enzyme, but its fluorescence is quenched by interaction with aromatic residues in the catalytic site, whereas bending of the duplex at the non-target site alleviates inter-base quenching and exposes the 2AP to solvent.


Electrochemical characterization of self-assembled monolayers (SAMs) of silanes on indium tin oxide (ITO) electrodes--tuning electron transfer behaviour across electrode-electrolyte interface.
In this work, we have systematically investigated the formation and characterization of Self-assembled Monolayer (SAM) films of several silanes on indium tin oxide (ITO) surfaces. Silane molecules having different domains namely substrate binding domain (siloxanes), electron transport region (aliphatic and aromatic spacer) and terminal functional groups (-SH, -CH(3) groups) are employed for the study in order to tune the electron transfer (ET) behaviour across SAM modified electrode-electrolyte interface. Structural characterization of these monolayer films is carried out using X-ray photoelectron spectroscopy (XPS) studies. Wettability (hydrophilic and hydrophobic nature) of such modified electrodes is evaluated using contact angle measurements. ET behaviour of these modified electrodes is investigated by electrochemical techniques namely cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) using K(4)Fe(II)(CN)(6)|K(3)Fe(III)(CN)(6) redox couple as a probe. Disappearance of redox peaks in the CV measurements and formation of semicircle having a higher charge transfer resistance (R(ct)) values during EIS studies suggest that the resultant monolayer films are compact, highly ordered with very low defects and posses good blocking property with less pinholes. The heterogeneous ET rate constant (k) values are determined from EIS by fitting them to an appropriate equivalent circuit model. Based on our results, we comment on tuning the ET behaviour across the interface by a proper choice of spacer region.


Comparative distribution of vasoactive intestinal polypeptide (VIP), substance P and PHI in the enteric sphincters of the cat.
In the feline gastrointestinal tract, the neuropeptides, substance P, VIP and PHI were investigated by specific radioimmunoassays and immunocytochemistry. The concentrations of all 3 peptides and the level of peptidergic innervation were significantly less in the anal sphincter than elsewhere, whereas no significant differences were seen between other sphincter and non-sphincter regions.


Venous thromboembolism prophylaxis in traumatic brain injury patients: An audit of clinical practice in AlRass General Hospital, Saudi Arabia and proposal for future clinical practice.
To review clinical practice with regards to venous thromboembolism prophylaxis in traumatic brain injury patients and to propose guidelines. The retrospective study was conducted at Al Rass General Hospital, Saudi Arabia, and comprised medical records of all traumatic brain injury patients admitted to the Neurosurgery Department between November, 2017, and January, 2018. Data was noted using a proforma. Literature review was done to ascertain best clinical evidence and proposed guidelines for practice. Of the 26 patients, 23(88.5 %) were males, and 3(11.5 %) were females. The overall mean age was 32.2±13.4 years. Of the total, 8(30.8%) patients had mechanical venous thromboembolism prophylaxis, while 1(3.8%) received enoxaparin as chemoprophylaxis. There were no reported thromboembolic events or complications related to enoxaparin usage. The usage of venous thromboembolism prophylaxis was found to be low in clinical practice. A modified Parkland Model approach seemed the most appropriate to avoid venous thromboembolism related events.


Outcome of patients having heart transplantation for lymphocytic myocarditis.
Heart transplantation (HT) for myocarditis has been controversial because of earlier reports of a poor prognosis after the procedure. We sought to determine whether lymphocytic myocarditis (LM) at the time of HT affects cardiac allograft rejection and survival after HT compared with other patients without LM in the current era of HT. We retrospectively reviewed 759 consecutive patients who underwent de novo HT at Columbia University Medical Center between 2000 and 2010 and compared prognosis after HT of the patients with pathologically proven LM in their explanted hearts with that of age- and gender-matched patients with idiopathic dilated cardiomyopathy (IDC group; n = 96) and with ischemic cardiomyopathy (IC group; n = 64). Thirty-two patients (4.2%) had LM in the explanted hearts pathologically. Among the 3 groups, no statistically significant difference was observed in the number of biopsy-diagnosed acute cellular rejection (ACR; International Society for Heart & Lung Transportation grade ≥2R) events during the first year after HT. In contrast, the frequency of biopsy-diagnosed ACR in subsequent years was greater in the LM group (n = 8, 3.8%) than in IC group (n = 3, 0.5%, p = 0.006), although no different from that of patients with IDC. The frequency of antibody-mediated rejection and posttransplant survival did not differ among the 3 groups. In conclusion, patients with pre-HT LM have an increased frequency of late ACR after HT compared with patients with IC. Nevertheless, survival of LM patients after HT is comparable to that of patients transplanted for IDC or IC.


Phosphorylation of rod outer segment proteins modulates phosphatidylethanolamine N-methyltransferase and phospholipase A2 activities in photoreceptor membranes.
The activities of enzymes involved in lipid metabolism--phospholipase A2 (PLA2) and phosphatidylethanolamine N-methyltransferase (PE N-MTase)--were found to be differently affected by pre-incubation of rod outer segments (ROS) under protein phosphorylating or dephosphorylating conditions. Exposure to cAMP-dependent protein kinase (PKA), under dark or light conditions, produced a significant increase in PE N-MTase activity, whereas PLA2 activity decreased. Under standard protein kinase C (PKC) phosphorylating conditions in light, PE N-MTase activity was stimulated and PLA2 activity was not affected. When the assays were performed in the dark, both enzymatic activities were unaffected when compared to the corresponding controls. Incubation of ROS membranes in light in the presence of PKC activators phorbol 12,13-dibutyrate (PDBu) and dioctanoylglycerol (DOG) resulted in the same pattern of changes in enzyme activities as described for standard PKC phosphorylating condition. Pre-incubation of membranes with the PKC inhibitor H-7 reduced the stimulation of PDBu on PE N-MTase activity, and had no effect on PLA2 activity in ROS membranes incubated with the phorbol ester. Pre-treatment of isolated ROS with alkaline phosphatase resulted in decreased PE N-MTase activity and produced a significant stimulation of PLA2 activity under dark as well as under light conditions when compared to the corresponding controls. These findings suggest that ROS protein phosphorylation and dephosphorylation modulates PE N-MTase and PLA2 activities in isolated ROS, and that these activities are independently and specifically modulated by particular kinases. Furthermore, dephosphorylation of ROS proteins has the opposite effect to that produced by protein phosphorylation on the enzymes studied.


Syntheses of new modified Phe-Pro peptides. Use of proline replacements in potential HIV inhibitors.
The syntheses consisting of replacement of proline amino acid by a 3-pyrrolidinone ring in Phe-Pro analogues are described. Preliminary anti-HIV studies demonstrated the potential activity of this new class of compounds.


Repeat intramuscular transplantation of human dental pulp stromal cells is more effective in sustaining Schwann cell survival and myelination for functional recovery after onset of diabetic neuropathy.
Mesenchymal stromal cell (MSC) therapy for diabetic neuropathy (DN) has been extensively researched in vitro and in pre-clinical studies; however, the clinical scenario thus far has been disappointing. Temporary recovery, a common feature of these studies, indicates that either the retention of transplanted cells deteriorates with time or recovery of supportive endogenous cells, such as bone marrow-derived MSCs (BM-MSCs), does not occur, requiring further replenishment. In DN, BM-MSCs are recognized mediators of Schwann cell regeneration, and we have earlier shown that they suffer impairment in the pre-neuropathy stage. In this study, we attempted to further elucidate the mechanisms of functional recovery by focusing on changes occurring at the cellular level in the sciatic nerve, in conjunction with the biodistribution and movement patterns of the transplanted cells, to define the interval between doses. We found that two doses of 1 × 106 dental pulp stromal cells (DPSCs) transplanted intramuscularly at an interval of 4 weeks effectively improved nerve conduction velocity (NCV) and restored motor coordination through improving sciatic nerve architecture, Schwann cell survival and myelination. Despite very minimal recovery of endogenous BM-MSCs, a temporary restoration of NCV and motor function was achieved with the first dose of DPSC transplantation. However, this did not persist, and a repeat dose was needed to consolidate functional improvement and rehabilitate the sciatic nerve architecture. Thus, repeat intramuscular transplantation of DPSCs is more effective for maintenance of Schwann cell survival and myelination for functional recovery after onset of DN.


[Comparison of CT, scintigraphy, and angiography in the topographic and pathological diagnosis of 300 supratentorial tumors (author's transl)].
The results of CT, scintigraphy (CSS), and angiography in 300 supratentorial cerebral tumors were compared with regard to the topographic and pathological diagnosis proposed in the initial reports. CT elucidated the topography in 98% of the cases and the pathology in variable percentages, depending on the type of tumor. The use of scintigraphy provided a high accuracy of pathological diagnosis. Except for meningiomas, arteriography was less accurate than the two other methods of examination. A radiological management of supratentorial cerebral tumors is proposed based on clinical and CT data.


Associations of SNAP-25 polymorphisms with cognitive dysfunctions in Caucasian patients with schizophrenia during a brief trail of treatment with atypical antipsychotics.
The synaptosomal-associated protein of 25 kDa (SNAP-25) is part of the soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment receptor (SNARE), which mediates synaptic neurotransmission. In earlier studies a possible involvement of this protein in schizophrenia has been shown. As neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be a putative endophenotype according to genetic studies we investigated the influences of different SNAP-25 polymorphisms on neuropsychological test results before and during treatment with atypical antipsychotics. A total of 104 schizophrenic patients treated with atypical antipsychotics were genotyped for three different polymorphisms of the SNAP-25 gene (MnlI, TaiI and DdeI in the 3'-UTR). Cognitive function was assessed at baseline, week 4 or 6 and week 8 or 12. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. The MnlI and TaiI polymorphisms showed no associations to deficits on neuropsychological test results. In contrast, we observed a significant relation between the DdeI polymorphism of the SNAP-25 gene and cognitive dysfunctions. Homozygote T/T allele carriers of the DdeI polymorphism showed significant better neuropsychological test results in cognitive domains verbal memory and executive functions than those with the combined T/C and C/C genotypes (P < 0.01) at all three time points, but no differences in response to treatment with atypical antipsychotics. Additionally, TT carriers exhibited significantly better results in a general cognitive index (P < 0.05). As we observed an association between the DdeI polymorphism of the SNAP-25 gene and cognitive dysfunctions of schizophrenic patients our finding suggests that the SNAP-25 gene could play a role in the pathophysiology of neurocognitive dysfunctions in schizophrenia but is not predictive for treatment response with atypical antipsychotics.


Constrained circulation at Endeavour ridge facilitates colonization by vent larvae.
Understanding how larvae from extant hydrothermal vent fields colonize neighbouring regions of the mid-ocean ridge system remains a major challenge in oceanic research. Among the factors considered important in the recruitment of deep-sea larvae are metabolic lifespan, the connectivity of the seafloor topography, and the characteristics of the currents. Here we use current velocity measurements from Endeavour ridge to examine the role of topographically constrained circulation on larval transport along-ridge. We show that the dominant tidal and wind-generated currents in the region are strongly attenuated within the rift valley that splits the ridge crest, and that hydrothermal plumes rising from vent fields in the valley drive a steady near-bottom inflow within the valley. Extrapolation of these findings suggests that the suppression of oscillatory currents within rift valleys of mid-ocean ridges shields larvae from cross-axis dispersal into the inhospitable deep ocean. This effect, augmented by plume-driven circulation within rift valleys having active hydrothermal venting, helps retain larvae near their source. Larvae are then exported preferentially down-ridge during regional flow events that intermittently over-ride the currents within the valley.


Mobile NMDA receptors at hippocampal synapses.
Glutamate receptors are concentrated in the postsynaptic complex of central synapses. This implies a highly organized and stable postsynaptic membrane with tightly anchored receptors. Recent reports of rapid AMPA receptor insertion and removal at synapses have challenged this view. We examined the stability of synaptic NMDA receptors on cultured hippocampal neurons using the open-channel blockers (+)-MK-801 and ketamine to tag synaptic NMDA receptors. NMDA receptor-mediated EPSCs showed an anomalous recovery following "irreversible" MK-801 block. The recovery could not be attributed to MK-801 unbinding or insertion of new receptors, suggesting that membrane receptors had moved laterally into the synapse. At least 65% of synaptic NMDA receptors were mobile. Our results indicate that NMDA receptors can move laterally between synaptic and extrasynaptic pools, providing evidence for a dynamic organization of synaptic NMDA receptors in the postsynaptic complex.


Unconjugated and conjugated bilirubin pigments during perinatal development. IV. The influence of breast-feeding on neonatal hyperbilirubinemia.
One thousand four hundred and fifty-four consecutive full-term neonates, delivered over a period extending from February 1, 1991 to January 31, 1992 were prospectively studied during the first days of life to determine if breast-feeding and hyperbilirubinemia were related. Six hundred and five infants were exclusively breast-fed on demand, 623 received both breast- and formula-feeding, and 226 were exclusively formula-fed. Of the 1,454 newborns studied, 70 (4.8%) presented with a bilirubin serum concentration > 12.9 mg/dl (4.62% in the breast-fed group, 5.45% in the group fed with mother's milk with supplements, and 3.54% in the artificial formula group; the differences were not significant). Percent mean weight losses on the 3rd and 5th days were not significantly different. Babies breast-fed on demand seem to have a low incidence of hyperbilirubinemia similar to that found in formula-fed neonates.


Prolyl 3-hydroxylase and 4-hydroxylase activities in certain rat and chick-embryo tissues and age-related changes in their activities in the rat.
Prolyl 3-hydroxylase activity, expressed per unit of extract protein, was much higher in rat kidney cortex than in the lung, liver or skin. A marked decrease in activity was found in the kidney cortex, liver and skin beyond 10 days of age. The ratio of prolyl 3-hydroxylase to 4-hydroxylase activity in the kidney cortex was 13--17 times that in the skin, that in the liver 6--8 times, and that in the lung about twice the value for the skin, there being no changes in this ratio with age. In 16-day chick embryos the highest ratios of prolyl 3-hydroxylase to 4-hydroxylase activity were found in the liver, heart, lens, aorta and kidney, and the lowest ratios in tendon, cartilage, cartilaginous and membranous bone and skin. The results suggest that the differences in the extent of prolyl 3-hydroxylation between various collagens can in part be explained by differences in the amount of prolyl e-hydroxylase activity among different cells.


Cisplatin and radiation in the treatment of tumors of the central nervous system: pharmacological considerations and results of early studies.
To review the human central nervous system pharmacology of cisplatin, factors that affect cisplatin uptake in tumors, and use alone and with radiation for the treatment of primary brain tumors. The authors review their own prior published and unpublished experience and data published by other groups on the above issues. Cisplatin is one of the most active chemotherapy drugs available for the treatment of solid tumors. It is synergistic with several other agents, including radiation. While it attains only low concentrations in the normal central nervous system, concentrations and plasma-tissue transfer constants for human intracerebral tumors are comparable to those in extracerebral tumors. Tumor type appears to be a more important determinant of platinum concentration than is tumor location, and gliomas do achieve lower concentrations than do other intracerebral or extracerebral tumors. Several other factors have also been identified that correlate with concentrations of cisplatin achieved in human tumors. While cisplatin alone and in combination with other drugs does have some degree of efficacy against primary brain tumors, combining it with cranial irradiation has generally not resulted in any substantial improvement in outcome to date, although some individual studies have been somewhat encouraging. New approaches are currently under investigation. Human pharmacology studies provide a rationale for use of cisplatin in the treatment of human brain tumors, and human and in vitro studies suggest some manipulations that might potentially further augment tumor platinum concentrations. While clinical studies suggest that cisplatin combinations may be of some value vs. human primary brain tumors and brain metastases, and while in vitro studies suggest that cisplatin potentiates radiation efficacy, no combination of cisplatin plus radiation yet tested has appeared to be superior to radiation alone.


Method for identifying putrefied corpses by facial casting.
The authors developed an original method for casting the face of putrefied corpses, which allowed a three-dimensional facial cast of an individual to be made. This method used several stages: face restoration by subcutaneous injections of specific materials, casting by elastomer, then three-dimensional positive image building. This technique enabled the person to be recognized and then identified, and seems to be useful in such difficult cases.


Solvent influence on the phase behavior and glass transition of Amorphous Solid Dispersions.
Understanding the long-term stability of amorphous solid dispersions (ASDs) is important for their successful approval for market. ASD stability does not only depend on the interplay between the active pharmaceutical ingredient (API) and the polymer in the final formulation but may already be disadvantageously influenced by process steps during the production (e.g. selection of inappropriate solvent for spray drying). Residual solvent can affect the API solubility in the polymer, molecular mobility (by influencing the glass-transition temperature) and induce liquid-liquid phase separation. Enhanced mobility in the ASD due to residual solvent can promote recrystallization in ASDs. The removal of residual solvent can be expensive, time-consuming, and usually requires secondary drying procedures to fulfil the regulatory requirements. The aim of this work is to predict the API solubility in polymer-solvent mixtures, solvent influence on the glass transition, and the occurrence of liquid-liquid phase separation of solvent-loaded ASDs using the thermodynamic model PC-SAFT and to experimentally validate these predictions. ASDs containing the APIs ritonavir or naproxen and the polymers poly(vinylpyrrolidone), poly (vinylpyrrolidone-co-vinyl acetate), or hydroxypropyl methylcellulose acetate succinate were spray-dried using the solvents acetone, ethanol, and dichloromethane. API solubility, sorption behavior, liquid-liquid phase separation and glass transition in the ternary API/polymer/solvent mixtures were predicted based on the binary phase behavior between API/solvent, API/polymer, and polymer/solvent and successfully validated experimentally using dynamic vapor sorption (DVS), and Raman spectroscopy. Thus, the presented methodology allows for an in-silico selection of appropriate solvent systems for solvent-based ASD preparation based on a limited amount of experimental data for binary systems only.


Gamma interferon-like immunoreactivity in the rat nervous system.
The presence of gamma interferon-like immunoreactivity in the peripheral nervous system and in some central nervous system neurons is described. The immunohistochemical evidence is based upon labeling of neurons with five different monoclonal antibodies against rat gamma interferon and one polyclonal antiserum. Immunoreactive material was abundantly present in the peripheral nervous system including small primary sensory neurons in dorsal root ganglia and postsynaptic neurons of the sympathetic and parasympathetic nervous system. Large neurons in dorsal root ganglia were not stained. Neurites stained with DB1 antibody against rat gamma interferon were found in most organs examined such as the gastrointestinal tract, heart, lungs, kidney, sexual organs and skin. In contrast, staining was weak in the central nervous system and restricted to a few neurons in the hypothalamus and in the midbrain. It is speculated that this newly discovered system containing a gamma interferon-like neuropeptide could be involved in the neuronal control of immunological processes in its target organs.


A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients. We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI. The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p < 2e - 16), and 1.2 SD higher in the young patients compared with the old (p = 3e - 4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies. The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.


Quantifying the Risk of Drug-Induced Pancreatitis With Angiotensin-Converting Enzyme Inhibitors and Statins Using a Large Electronic Medical Record Database.
Quantify the risk of drug-induced pancreatitis (DIP) from angiotensin-converting enzyme inhibitors (ACEis) and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins). Retrospective cohort analysis using IBM Explorys (1999-2019), a pooled, deidentified clinical database of more than 63 million patients across the United States. Odds ratios were calculated to determine the risk of DIP from ACEi, statins, and both medications together. χ2 testing assessed the relationship between age, sex, ethnicity, insurance status, and mortality among patients with DIP from ACEi, statins, or both combined. Acute pancreatitis (AP) was found in 280,740 patients. Odds ratios for ACEi, statins, and both combined were 6.12, 4.97, and 5.72, respectively. Thirty-eight percent of all-cause AP occurs in adults older than 65 years. Acute pancreatitis from ACEi and statins occurs in 49% and 56% of patients older than 65 years, respectively. Men and patients older than 65 years are at higher risk of DIP from ACEi and statins. Patients on Medicaid are at higher risk of DIP from statins, and Asian patients are at highest risk of DIP from ACEi. We found that ACEi and statins increase the odds of DIP. Although ACEis and statins are critical medications for many patients, clinicians should consider using alternatives in patients with AP of unclear etiology.


Dissection of a novel molecular determinant mediating Golgi to trans-Golgi network transition.
Two major functions of the Golgi apparatus (GA) are formation of complex glycans and sorting of proteins destined for various subcellular compartments or secretion. To fulfill these tasks proper localization of the accessory proteins within the different sub-compartments of the GA is crucial. Here we investigate structural determinants mediating transition of the two glycosyltransferases beta-1,4- galactosyltransferase 1 (gal-T1) and the alpha-1,3-fucosyltransferase 6 (fuc-T6) from the trans-Golgi cisterna to the trans-Golgi network (TGN). Upon treatment with the ionophore monensin both glycosyltransferases are found in TGN-derived swollen vesicles, as determined by confocal fluorescence microscopy and density gradient fractionation. Both enzymes carry a signal consisting of the amino acids E(5)P(6) in gal-T1 and D(2)P(3) in fuc-T6 necessary for the transition of these glycosyltransferases from the trans-Golgi cisterna to the TGN, but not for their steady state localization in the trans-Golgi cisterna.


A new synthesis of symmetric boraindacene (BODIPY) dyes.
BODIPY dyes were synthesized from pyrrole-2-carbaldehyde derivatives in high yields; this constitutes a new approach to this dye framework.


Characteristics of International Assaultive Psychiatric Patients: Review of Published Findings, 2013-2017.
Since the 1960s, empirical research has worked toward a better understanding of the characteristics of assaultive psychiatric patients. International research through 2012 indicated that male and female patients with schizophrenia and other diagnoses presented the greatest risk for assault. This present review of studies that presented raw assault sought to assess the latest research findings on assaultive patients for the most recent 5 year period, 2013-2017. It was hypothesized that male patients with schizophrenia would present the greatest risk. The findings indicated a sharp increase in the total number of reported assault incidents over the proceeding decade. These assaults were committed largely by male patients with a diagnosis of schizophrenia. Explanations for these findings and an updated methodological inquiry are presented.


Ethical decisions in perioperative elder care.
Settings involving the extremes of age and illness are the most complex in ethical deliberation and require sound principles that can be clearly applied to individual situations. This article discusses how one's view of the aging process effects clinical decision making. The basic principles of medical ethics (autonomy, beneficence, nonmaleficence, and justice) are discussed along with alternative ethical paradigms that may be more appropriate to the elderly population. Issues such as informed consent, do not resuscitate orders in the operating room, and controversies in end-of-life palliative care specifically impact the role of the anesthesiologist. Anesthesiologists, as medical professionals in a health care team, have a great stake in ethical decision making and the ethics of health care policy.


Novel, vessel anatomy adjusting drug-coated balloon-Preclinical evaluation in peripheral porcine arteries.
The diameter of balloons or stents is selected according to the estimated reference vessel diameter and do not adapt to the vessel anatomy. The aim of the present preclinical studies was to investigate a novel, vessel anatomy adjusting hypercompliant drug-coated balloon catheter (HCDCB). Hypercompliant balloon membranes were coated in a constricted state with high drug density. Drug adherence was investigated in vitro, transfer to the porcine peripheral arteries and longitudinal distribution in vivo. In young domestic swine, neointimal proliferation was induced by vessel overstretch and continuous irritation by permanent stents. Uncoated hypercompliant balloons (HCB), and standard uncoated balloons and drug-coated balloons (DCB) served as controls. Efficacy was assessed by angiography, optical coherence tomography (OCT), and histomorphometry. HCDCB lost 18.0 ± 3.9% of dose during in vitro simulated delivery to the lesion. Drug transfer to the vessel wall was 13.9 ± 6.4% and drug concentration was 1,044 ± 529 ng/mg tissue. Four weeks after treatment, the histomorphometric neointimal area was smaller with HCDCB versus uncoated HCB (2.39 ± 0.55 mm2 vs. 3.26 ± 0.72 mm2 , p = .038) and area stenosis (OCT) was less (11.6 ± 6.9% vs. 24.7 ± 9.7%, p = .022). No premature death occurred and no in-life clinical symptoms or treatment-associated thrombi were observed. HCDCB were found to inhibit excessive neointimal proliferation. Balloon adaption to different vessel diameters and shapes may provide drug-delivery in irregular lumen and facilitate balloon selection.


Surgical Outcomes in 62 Patients with Ulcerative Colitis: A Retrospective, Single-Center Study from Poland.
BACKGROUND Surgery continues to play an important role in the treatment of ulcerative colitis (UC), which is one of the most common inflammatory diseases of the colon and rectum. This retrospective study from a single center in Poland aimed to evaluate surgical outcomes in 62 patients with ulcerative colitis. MATERIAL AND METHODS The study enrolled 62 patients (36 men [58.1%], 26 women [41.9%]), mean age 52.69±16.84 (range, 19-96) years who underwent surgical treatment of UC during the period 2001-2020. The mandatory inclusion criteria were patients with UC, who underwent total intra-abdominal colectomy (n=22, 46.8%), proctocolectomy (n=25, 53.2%), or left-sided hemicolectomy (n=8, 12.9%). The primary endpoint was postoperative death, and secondary endpoints were long hospitalization (>15 days), complications, and relaparotomy. RESULTS Postoperative mortality was observed in 8 (12.9%) patients. Older age and low albumin level were associated with longer hospitalization time (P=0.004 and P<0.001, respectively). High C-reactive protein (CRP) level (P=0.003), high CRP/albumin ratio (P=0.023), and malnourishment (P=0.026) were risk factors for complications. Malnutrition (P=0.026), older age (P=0.031), high CRP level (p<0.001), high CRP/albumin ratio (P=0.014), arterial hypertension (P=0.012), and urgent surgeries (P=0.021) were associated with higher risk of postoperative death. Patients who had undergone previous surgeries were more likely to need relaparotomy (P=0.022). CONCLUSIONS Preoperative nutritional status was an important factor associated with postoperative outcomes in patients with ulcerative colitis. Correction of malnutrition seems to be a vital part of preoperative preparation.


Ultrasound detection of first trimester malformations: a pictorial essay.
Knowledge of normal and abnormal anatomy in the first trimester aids in early detection of anomalies and the avoidance of potential pitfalls.


Probing metallo-β-lactamases with molecular fragments identified by consensus docking.
Bacterial resistance mediated by metallo-β-lactamases (MBLs) is a major problem for the treatment of infections. An MBL inhibitor could restore the potency of β-lactam antibiotics. Fragment-based design might deliver valuable starting points for the discovery of novel MBL inhibitors. In this study, we chose an in silico approach to search for fragments able to bind and inhibit NDM-1, VIM-1, and IMP-7. We used consensus docking to identify low molecular weight compounds from a commercially available library. Most promising compounds were evaluated in a sensitive fluorescence-based activity assay and by the orthogonal biophysical technique saturation transfer difference (STD)-NMR. (1)H-(15)N chemical shift perturbation NMR was used to confirm the reversible binding and measure the dissociation constant of the most promising compound qualifying it as a high-quality starting point for further optimization.


Comparison of three analytical methods for superoxide produced by activated immune cells.
Superoxide plays a key role in normal immune function and inflammatory diseases. In order to evaluate normal immune function or screen inhibitors of superoxide production for treating inflammatory diseases, it is very important to detect superoxide with good accuracy, sensitivity, and flexibility. In present study, we investigated three analysis methods of superoxide, colorimetric assay by WST-8, fluorescence assay by dihydroethidium and chemiluminescence assay by lucigenin, compared their precisions, specificities, sensitivities and time curve characteristics in superoxide analysis, and then validate their values in the screening of anti-inflammatory compounds. The results reveal that three analysis methods of superoxide all have good precisions and high specificities but have different sensitivities and time curve characteristics, which suggest their different applications. In addition, they can all be used in the screening of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors and anti-inflammatory compounds.


[Aneurysmal cysts of the fronto-parietal bone].
The authors describe the case of a patient affected by an aneurysmal bone cyst of the fronto-parietal bone. A short review of the literature follows.


Modeling microalgal growth in an airlift-driven raceway reactor.
In previous proof-of-concept studies, feasibility of a new airlift-raceway configuration and its energetic advantage and improved CO2 utilization efficiency over the traditional raceways and photobioreactors have been documented. In the current study, a mathematical model for predicting biomass growth in the airlift-raceway reactor is presented, which includes supply and transfer of CO2 and the synergetic effects of light, CO2, nitrogen, and temperature. The model was calibrated and validated with data from prototype scale versions of the reactor on two test species: Nannochloropsis salina and Scenedesmus sp., cultivated under indoor and outdoor conditions. Predictions of biomass concentrations by the proposed model agreed well with the temporal trend of the experimental data, with r(2) ranging from 0.96 to 0.98, p<0.001. A sensitivity analysis of the 10 model parameters used in this study revealed that only three of them were significant, with sensitivity coefficients ranging from 0.08 to 0.13.


CD157 signaling promotes survival of acute myeloid leukemia cells and modulates sensitivity to cytarabine through regulation of anti-apoptotic Mcl-1.
CD157/BST-1 (a member of the ADP-ribosyl cyclase family) is expressed at variable levels in 97% of patients with acute myeloid leukemia (AML), and is currently under investigation as a target for antibody-based immunotherapy. We used peripheral blood and bone marrow samples from patients with AML to analyse the impact of CD157-directed antibodies in AML survival and in response to cytarabine (AraC) ex vivo. The study was extended to the U937, THP1 and OCI-AML3 AML cell lines of which we engineered CD157-low versions by shRNA knockdown. CD157-targeting antibodies enhanced survival, decreased apoptosis and reduced AraC toxicity in AML blasts and cell lines. CD157 signaling activated the PI3K/AKT/mTOR and MAPK/ERK pathways and increased expression of Mcl-1 and Bcl-XL anti-apoptotic proteins, while decreasing expression of Bax pro-apoptotic protein, thus preventing Caspase-3 activation. The primary CD157-mediated anti-apoptotic mechanism was Bak sequestration by Mcl-1. Indeed, the Mcl-1-specific inhibitor S63845 restored apoptosis by disrupting the interaction of Mcl-1 with Bim and Bak and significantly increased AraC toxicity in CD157-high but not in CD157-low AML cells. This study provides a new role for CD157 in AML cell survival, and indicates a potential role of CD157 as a predictive marker of response to therapies exploiting Mcl-1 pharmacological inhibition.


Increased educational attainment and its effect on child mortality in 175 countries between 1970 and 2009: a systematic analysis.
In addition to the inherent importance of education and its essential role in economic growth, education and health are strongly related. We updated previous systematic assessments of educational attainment, and estimated the contribution of improvements in women's education to reductions in child mortality in the past 40 years. We compiled 915 censuses and nationally representative surveys, and estimated mean number of years of education by age and sex. By use of a first-differences model, we investigated the association between child mortality and women's educational attainment, controlling for income per person and HIV seroprevalence. We then computed counterfactual estimates of child mortality for every country year between 1970 and 2009. The global mean number of years of education increased from 4·7 years (95% uncertainty interval 4·4-5·1) to 8·3 years (8·0-8·6) for men (aged ≥25 years) and from 3·5 years (3·2-3·9) to 7·1 years (6·7 -7·5) for women (aged ≥25 years). For women of reproductive age (15-44 years) in developing countries, the years of schooling increased from 2·2 years (2·0-2·4) to 7·2 years (6·8-7·6). By 2009, in 87 countries, women (aged 25-34 years) had higher educational attainment than had men (aged 25-34 years). Of 8·2 million fewer deaths in children younger than 5 years between 1970 and 2009, we estimated that 4·2 million (51·2%) could be attributed to increased educational attainment in women of reproductive age. The substantial increase in education, especially of women, and the reversal of the gender gap have important implications not only for health but also for the status and roles of women in society. The continued increase in educational attainment even in some of the poorest countries suggests that rapid progress in terms of Millennium Development Goal 4 might be possible. Bill & Melinda Gates Foundation.


Crystallization and preliminary crystallographic analysis of a thermostable mutant of kanamycin nucleotidyltransferase.
A thermostable mutant of kanamycin nucleotidyltransferase isolated by cloning and selection for kanamycin resistance in Bacillus stearothermophilus at 70 degrees C has been crystallized in a form suitable for high-resolution diffraction analysis. This enzyme catalyzes nucleotidyl group transfer from nucleoside triphosphates such as ATP to hydroxyl groups of various aminoglycosides, thus inactivating the antibiotic. The kanamycin nucleotidyltransferase gene, originally encoded on plasmid pUB110 from the mesophile Staphylococcus aureus, was transferred to the thermophile B. stearothermophilus via shuttle plasmids and the mutant carrying the substitutions D80Y and T130K was isolated from kanamycin-resistant colonies grown at 70 degrees C. The thermostable enzyme was crystallized in two forms from solutions of polyethylene glycol 8000 (PEG8000) using batch and vapor diffusion methods. Type I crystals grown from 19% (w/v) PEG8000 and 200 mM NaCl belong to the orthorhombic space group C222(1), have unit cell dimensions of a = 128.4, b = 156.8, c = 155.8 A, and diffract to at least 2.4-A resolution. The type II form of the crystals were grown from 10% PEG8000, 200 mM KCl, and 3 mM CoCl2, and belong to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions of a = b = 78.9, and c = 220.4 A; these crystals diffract to at least 2.5-A resolution.


Cytokine adsorption as a promising option for septic shock and multiple organ failure due to Candida infection and decompensated type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) represents one of the most common chronic diseases in childhood. It is associated with high morbidity and mortality rates due to metabolic dysregulation, immunosuppressive effects, and a predisposition to fungal infections. Candidiasis is a severe infection and its prevalence has increased throughout the last decades. We report the case of a 19-year-old female patient admitted to our intensive care unit with T1DM and Candida infection associated with severe metabolic acidosis. In the absence of response to high dose catecholamine cardiovascular therapy and the presence of severe metabolic acidosis, a CytoSorb cartridge was implemented into the extracorporeal dialysis circuit resulting in a stabilization of hemodynamics accompanied by a tremendous decrease in vasopressor requirements, control of the hyperinflammatory response, as well as a resolution of metabolic acidosis and regeneration of renal function. Treatment with CytoSorb was safe and feasible without technical problems. Notably, this is the first case description reporting on the effects of CytoSorb in a patient with Candida infection as part of T1DM.


Morphometric analysis of the capillary supply in skeletal muscles of trained and untrained subjects--its limitations in muscle biopsies.
Muscle fiber area, capillary density, and capillary to fiber ratio were determined in needle biopsy samples of M. vastus lateralis processed for electron microscopy from 9 untrained men (average VO2 max = 43.7 ml/min kg) and 5 well trained orienteers (VO2 max = 76.1 ml/min kg). The volume density of mitochondria was previously reported to be significantly higher in orienteers (7.32%) than in untrained men (5.19%) and in untrained women (4.08%) in the same material (Hoppeler et al. 1973). The mean fiber area was found to be somewhat larger in orienteers (6,410 microns 2) than in untrained men (5,350 microns 2, not significant), but significantly smaller values were found in untrained women (3,390 microns 2). The capillary density was almost identical in the three experimental groups, it ranged from 416 to 431 mm-2. The absolute values reported for both of the above variables are subjected to a bias due to fiber shrinkage, fiber shortening and fiber kinking occurring during the needle biopsy procedure and the subsequent steps of tissue preparation. The capillary to fiber ratio is much less affected by tissue handling and significantly higher values were found in orienteers (2.70) than in untrained men (2.07) and in untrained women (1.37). There was a significant linear relationship between the capillary to fiber ratio and both VO2 max and the volume density of mitochondria for all subjects analysed, suggesting an adjustment of the capillary supply to the maximal aerobic capacity as well as to the mitochondrial content in M. vastus lateralis.


Thalamic Ventral Intermediate Nucleus Deep Brain Stimulation for Orthostatic Tremor.
Orthostatic tremor (OT) was first described in 1977. It is characterized by rapid tremor of 13-18 Hz and can be recorded in the lower limbs and trunk muscles. OT remains difficult to treat, although some success has been reported with deep brain stimulation (DBS). We report a 68-year-old male with OT who did not improve significantly after bilateral thalamic stimulation. Although some patients were described who improved after DBS surgery, more information is needed about the effect of these treatment modalities on OT, ideally in the form of randomized trial data.


Key points in surgical management of mandibular condylar fractures.
Mandibular condylar fractures are among the most common facial fractures and some of the most difficult to manage. Opinions about the management of mandibular condylar fractures differ among surgeons. With the implementation of new technology, an increased understanding of fracture management, and better functional and morphological outcomes reported in the literature, open reduction and internal fixation is becoming many surgeons' preferred choice for the treatment of condylar fractures. Because surgical treatment of such fractures is complex, certain factors must be considered to achieve satisfactory outcomes. In this article, we summarise six key points in the management of mandibular condylar fractures: virtual evaluation of condylar fracture, a suitable surgical approach, good reduction, stable internal fixation, repair of the articular disc, and restoration of the mandibular arch width. We believe that these points will help to improve the prognosis of mandibular condyle fractures.


Different origins of low- and high-frequency components (600 Hz) of human somatosensory evoked potentials.
Human median nerve somatosensory evoked potentials (SEPs) contain a low-amplitude (<500 nV) high-frequency (approximately 600 Hz) burst of repetitive wavelets (HFOs) which are superimposed onto the primary cortical response 'N20.' This study aimed to further clarify the cortical and subcortical structures involved in the generation of the HFOs. 128-Channel recordings were obtained to right median nerve stimulation of 10 right-handed healthy human subjects and in 7 of them additional to right ulnar nerve. Data were evaluated by applying principal component analysis and dipole source analysis. Different source evaluation strategies provided converging evidence for a cortical HFO origin, with two different almost orthogonally oriented generators being active in parallel, but with a phase shift of a quarter of their oscillatory period, while the low-frequency 'N20' is adequately modeled by one tangential dipole source. Median and ulnar derived low-frequency and HFO cortical sources show a somatotopic order. Additionally, generation of the HFOs was localized in subcortical, near-thalamic and subthalamic source sites. The near-thalamic dipole was located at significantly different sites in HFO and low-frequency data. The cortical HFO source constellation points to a 'precortical' source in terminals of thalamocortical fibers and a second intracortical HFO origin. Furthermore, HFOs are also generated at subcortical and even subthalamic sites. Near-thalamic, the HFO and low-frequency signals are generated or modulated by different neuron populations involved in the thalamocortical outflow.


Dynamic compression plating in treatment of the fractured, edentulous mandible.
The repair of a mandibular fracture in the edentulous patient can be a difficult surgical problem. A recent report of a large series of such cases by the University of Michigan disclosed a 20% rate of nonunion. Dynamic compression plating is particularly suited to the repair of fractures of the edentulous mandible as intermaxillary fixation is unnecessary, normal speech and diet are resumed immediately, and bone grafts can be used when necessary. This series of 36 plates used in the management of mandibular fractures in 24 edentulous patients is the largest series of its type reported thus far. No nonunion or other major complication occurred in this series. Because nonunion, delayed union, and the problems associated with intermaxillary fixation were avoided in this series, it is suggested that compression plating is a highly effective method for repair of fractured edentulous mandibles.


NIDDM in the cat: treatment with the oral hypoglycemic medication, glipizide.
The oral hypoglycemic medication, glipizide, provides a viable therapeutic alternative to conventional insulin therapy with a positive therapeutic response in approximately 50% of diabetic cats with non-insulin-dependent disease. Response to glipizide therapy or lack thereof usually is evident within the first 4 to 6 weeks of treatment. Adverse side effects occurred in less than 10% of patients. The existence of residual beta cell function is necessary for response to glipizide therapy. Predictors of response to glipizide therapy were not found. Identification and correction or control of existing insulin antagonistic disease processes, as well as, discontinuation of diabetogenic medications that may be contributing to insulin resistance is also important.