A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha2 globin gene variant (Hb Conakry).
A Guinean woman, heterozygous for haemoglobin (Hb) S, was studied because of episodes of marked anaemia, repeated typical metaphyseal painful crises and haemosiderosis. Her sickling syndrome resulted from the association of Hb S trait with a severe pyruvate kinase deficiency leading to a 2,3-DPG concentration of twice normal levels. Sequence of the PK-R gene revealed an undescribed mutation in the homozygous or hemizygous state within exon 5 (nucleotide 2670 C-->A), leading to the interchange of Ser 130 into Tyr (PK Conakry). In addition, the patient carried a new haemoglobin variant, Hb Conakry [alpha80(F1) Leu-->Val], which seemed to have a mild effect. The high intraerythrocytic 2,3-DPG concentration induced by the PK deficiency resulted in a decreased oxygen affinity which favoured sickling to a level almost similar to that of Hb S/C compound heterozygous patients. This was confirmed by oxygen binding measurements of Hb A/Hb S erythrocytes in which 2,3-DPG content was modified in vitro. Hysteresis between deoxy- and reoxygenation curves, as well as increase in the n(max) value, demonstrated that the extent of HbS polymerization in the propositus was almost the same as that of RBCs from a homozygous sickle cell patient or those of an A/S heterozygous patient with an artificial in vitro increase of 2,3-DPG concentration.


The new bone WB-SPECT/CT: hybrid, from head-to-toe and digital! Is it worth the effort?
A bone scan (BS) plays a pivotal role in many oncological and non-oncological conditions. The planar BS is characterized by high sensitivity but low specificity. With respect to planar imaging, the implementation of single-photon emission computed tomography (SPECT) has allowed increased image contrast and more accurate tracer localization. Recent technological innovations in the field of BS are treated, with a particular focus on multi-field-of-view devices allowing to cover the entire scan length with a 3D acquisition (WB-SPECT/CT). In addition, the applications of cadmium zinc telluride/CzT detectors capable of converting gamma photons directly into electrical impulses (i.e. 'digital SPECT') are discussed. Initial clinical experiences indicate that WB-SPECT/CT is characterized by higher sensitivity, diagnostic accuracy, and increased confidence in image interpretation with respect to the 'old-fashioned' BS (planar images with or without a single field-of-view SPECT). Furthermore, CzT-based detectors, thanks to their superior sensitivity, might be helpful to implement fast acquisition protocols. Further studies are needed to better define the clinical impact of bone CzT WB-SPECT/CT on patients' management and outcome, as well as its cost-benefit ratio.


Dedifferentiation of human epidermal melanocytes into melanoblasts in vitro.
Melanoblasts (MB) are also called melanocyte (MC) precursor cells. In recent years, people have successfully cultivated human and mouse MB. Previous studies have shown that EDN3 induces cultivated bird MC to re-differentiate into double potential progenitor cells of MB. However, no study has reported whether in vitro cultivated human MC can be dedifferentiated. Our research on MC that were purified and cultivated in vitro found that adding 10 nm endothelin 1 (EDN1) (ET-1) to the MC medium without phorbol 12-myristate 13-acetate (PMA) induced a few MC to dedifferentiate and become a new type of cell. This new cell type was separated, purified, cloned and identified using multiple approaches. The results show that 88.7%, 8.69% and 2.5% of this new cell type were cells in the G(0) -G(1) , G(2) -M and S stages, respectively. The new cell type did not exhibit an apparent apoptotic peak, and its apoptotic rate was 0.09%. Stage I melanosomes were observed in the cytoplasm and were negative for the DOPA reaction. The cell surface antigen expression was positive for tyrosinase-related protein 2, negative or positive for c-kit and negative for S-100 and HMB45, showing that these cells were dedifferentiated MB of MC. Our findings provided evidence for atavism of mature human MC under certain conditions.


Oxygen free radical-mediated selective endothelial dysfunction in isolated coronary artery.
To understand the direct involvement of free radicals causing reduction in endothelium-dependent relaxation of isolated canine coronary ring preparations, this study was undertaken to examine the effect of free radicals generated from dihydroxy fumarate (DHF) plus Fe(3+)-ADP or from H2O2 plus FeSO4. The vasodilators (acetylcholine, bradykinin, A23187, and nitroglycerin) were given after DHF/Fe(3+)-ADP or H2O2/FeSO4 was removed from the organ chamber. The earlier DHF/Fe(3+)-ADP exposure produced an attenuation of the relaxation of the rings induced by acetylcholine, bradykinin, or A23187 but not of the relaxation induced by nitroglycerin. The observed effect of previous DHF/Fe(3+)-ADP exposure was significantly protected in the vessels isolated from the dogs treated with alpha-tocopherol. In the experiments for assessing the effect of various scavengers, 1O2 scavenger histidine or iron chelator deferoxamine effectively protected the attenuation induced by DHF/Fe(3+)-ADP exposure of the relaxation elicited by acetylcholine; superoxide dismutase (SOD), catalase, or dimethyl sulfoxide (DMSO) had no effect on this system. Furthermore, the relaxation elicited by acetylcholine, but not nitroglycerin, was significantly attenuated by the earlier exposure to .OH generated by Fenton's reagent (H2O2+FeSO4); the attenuation was significantly protected by DMSO. These results are consistent with the view that .OH, 1O2, and/or iron-dependent reactive species selectively damage endothelium-dependent relaxation as opposed to endothelium-independent relaxation in endothelium-intact coronary ring preparations. It is also postulated that lipid peroxidation may be responsible for this effect.


DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets.
Diabetic retinopathy (DR), a specific neuron-vascular complication of diabetes, is a major cause of vision loss among middle-aged people worldwide, and the number of DR patients will increase with the increasing incidence of diabetes. At present, it is limited in difficult detection in the early stages, limited treatment and unsatisfactory treatment effects in the advanced stages. The pathogenesis of DR is complicated and involves epigenetic modifications, oxidative stress, inflammation and neovascularization. These factors influence each other and jointly promote the development of DR. DNA methylation is the most studied epigenetic modification, which has been a key role in the regulation of gene expression and the occurrence and development of DR. Thus, this review investigates the relationship between DNA methylation and other complex pathological processes in the development of DR. From the perspective of DNA methylation, this review provides basic insights into potential biomarkers for diagnosis, preventable risk factors, and novel targets for treatment. DNA methylation plays an indispensable role in DR and may serve as a prospective biomarker of this blinding disease in its relatively early stages. In combination with inhibitors of DNA methyltransferases can be a potential approach to delay or even prevent patients from getting advanced stages of DR.


Evaluation of stroke health education for primary school students in Dali, China.
To provide us with some evidence to develop more targeted stroke intervention strategies, improve the health awareness of stroke among children, and advocate the health promotion campaign of "small hands holding big hands" among parents and children, we have conducted a health education program on stroke among primary school students in Dali. This study has applied stratified random cluster sampling in Dali of Yunnan, China. We compared the improvement of students' knowledge of stroke before and after our health education program in primary school students of Dali in October 2020. Data were collected through 3 rounds of survey by using the same questionnaire. There were 215 participants aged 7-8 years old sampled in the first phase of the study and 145 participants in the follow-up study. The knowledge of stroke among the participants was relatively low in the pre-intervention survey. After the health education, all the indicators on stroke knowledge were improved. The correct rates in stroke definition, sequelae, and "1-2-0" identification were increased from 0 to 66.05%, to 53.95% and 64.19%, respectively, in both pre-intervention and post-intervention surveys. The correct rate of stroke knowledge was about 4.83-92.41% 3 months after the intervention. The mean score of the questionnaire was 4.25 ± 0.19 in the pre-intervention survey, and that was 15.85 ±0.27 in the post-intervention one. The mean score was 14.02 ± 0.28 post-3-month test. The score in the 3-month survey after the intervention was 11.55% lower than that in the post-intervention score. The effect of stroke-related knowledge in the health education program for children is improved significantly and this can last for 3 months but it also had attenuation. We should repeat pertinent health education among students.


Mental Health System Reform in Contexts of Humanitarian Emergencies: Toward a Theory of "Practice-Based Evidence".
Humanitarian emergencies such as armed conflicts are increasingly perceived as opportunities to improve mental health systems in fragile states. Research has been conducted into what building blocks are required to reform mental health systems in states emerging from wars and into the barriers to reform. What is less well known is what work and activities are actually performed when mental health systems in war-affected resource-poor countries are reformed. Questions that remain unanswered are: What is it that international humanitarian aid workers and local experts do on the ground? What are the actual activities they perform in order to enable and sustain system reform? This article begins to answer these questions through ethnographic case studies of mental health system reform in Kosovo and Palestine. Based on the findings, a theory of "practice-based evidence" is developed. Practice-based evidence assumes that knowledge is derived from practice, rather than the other way around where practice is believed to be informed by systematic evidence. It is argued that a focus on practice rather than evidence can improving system reform processes as well as the provision of mental health care in a way that is sensitive to local contexts, structural realities, culture, and history.


Removal of Phenazopyridine from wastewater by merging biological and electrochemical methods via Azolla filiculoides and electro-Fenton process.
In the present study, the potential of Azolla filiculoides (A. filiculoides) was first investigated for degradation of Phenazopyridine (PhP), an analgesic drug. The effects of main variables such as initial pharmaceutical concentration, amount of plant, and pH were studied on the efficiency of the biological process. It was observed that A. filiculoides was able to remove pharmaceuticals from contaminated water up to 85.90% during 48 h. Then, the electro-Fenton (EF) method was applied for further removal of PhP yielding a removal rate of about 98.72% under optimum conditions during 2 h. The effects of variables including the current, amount of catalyst, and pH were also studied in this phase. Also, the probability of adsorption was investigated during this step. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis were performed for the used magnetite nanoparticles, total organic carbon (TOC) were performed to investigate PhP removal efficiency during the reaction time and Gas chromatography-mass spectrometry (GC-MS) were performed to analyze degradation byproducts of PhP. Based on the results, it was found that a combination of these bioremediation and electrochemical removal steps were capable of PhP removal from contaminated water. Therefore, this approach may be effective for phytoremediation of pharmaceutical-contaminated aquatic ecosystems.


Sibling psychological adjustment to type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) is a chronic condition whose management affects the whole family, and siblings of children with chronic conditions have been shown to be at higher risk of emotional and behavioural problems. The aims of this study were to investigate sibling adjustment to T1DM using a cross-sectional questionnaire survey design. Forty-one families (48% of those eligible) were recruited from a children's diabetes clinic. From each family, one parent and one sibling of the child with T1DM participated. Parents completed questionnaires measuring sibling adjustment and measures of major life events, social support and parenting stress. Demographic and disease information was obtained from medical records. Siblings completed questionnaires assessing cognitive appraisals and coping strategies. A semi-structured interview was also administered to siblings. Siblings were found to be better adjusted than normative data (p < 0.01). Factors associated with poorer sibling adjustment were higher sibling age at diagnosis, higher levels of parenting stress, more difficult sibling temperament, poorer adjustment of the child with T1DM, higher levels of parental distress and more negative sibling perceptions of diabetes and its impact on the family. Results suggest that sibling perceptions of diabetes and parental distress are important predictors of sibling adjustment to T1DM. The findings from this study emphasize the relationships between the adjustment of the sibling and that of the child with T1DM and their parents. Many parents worry about how the siblings may cope with the diabetes, but the results of this study are generally reassuring.


Closed-Loop Insulin Therapy Improves Glycemic Control in Adolescents and Young Adults: Outcomes from the International Diabetes Closed-Loop Trial.
Objective: To assess the efficacy and safety of closed-loop control (CLC) insulin delivery system in adolescents and young adults with type 1 diabetes. Research Design and Methods: Prespecified subanalysis of outcomes in adolescents and young adults aged 14-24 years old with type 1 diabetes in a previously published 6-month multicenter randomized trial. Participants were randomly assigned 2:1 to CLC (Tandem Control-IQ) or sensor augmented pump (SAP, various pumps+Dexcom G6 CGM) and followed for 6 months. Results: Mean age of the 63 participants was 17 years, median type 1 diabetes duration was 7 years, and mean baseline HbA1c was 8.1%. All 63 completed the trial. Time in range (TIR) increased by 13% with CLC versus decreasing by 1% with SAP (adjusted treatment group difference = +13% [+3.1 h/day]; 95% confidence interval [CI] 9-16, P < 0.001), which largely reflected a reduction in time >180 mg/dL (adjusted difference -12% [-2.9 h/day], P < 0.001). Time <70 mg/dL decreased by 1.6% with CLC versus 0.3% with SAP (adjusted difference -0.7% [-10 min/day], 95% CI -1.0% to -0.2%, P = 0.002). CLC use averaged 89% of the time for 6 months. The mean adjusted difference in HbA1c after 6 months was 0.30% in CLC versus SAP (95% CI -0.67 to +0.08, P = 0.13). There was one diabetic ketoacidosis episode in the CLC group. Conclusions: CLC use for 6 months was substantial and associated with improved TIR and reduced hypoglycemia in adolescents and young adults with type 1 diabetes. Thus, CLC has the potential to improve glycemic outcomes in this challenging age group. The clinical trial was registered with ClinicalTrials.gov (NCT03563313).


Angiotensin II stimulates both aldosterone secretion and DNA synthesis via type 1 but not type 2 receptors in bovine adrenocortical cells.
Angiotensin II (Ang II) type 2 receptor (AT2) has been shown to counteract the type 1 receptor (AT1)-mediated biological actions of Ang II in the cardiovascular system. The biological significance of AT2 receptor in the adrenals however remains unknown. In the present study, we investigated the roles of AT1 and AT2 receptor subtypes in the regulation of aldosterone secretion and DNA synthesis in bovine adrenocortical zona glomerulosa cells in vitro. Ang II (1 mumol/l)-stimulated aldosterone secretion was completely suppressed by AT1 antagonist CV-11974 but not affected by AT2 receptor antagonist PD-123319. Effects on DNA synthesis were investigated by determining the incorporation of BrdU into the nuclei of the cultured zona glomerulosa cells. Ang II (1 mumol/l)-stimulated DNA synthesis of the cells was also completely suppressed by CV-11974 but not by PD-123319. These results suggest that AT1 receptor but not AT2 receptor is the predominant receptor subtype which mediates the Ang II-stimulated aldosterone secretion and cell growth in bovine adrenocortical cells.


The relationship of platelet yield, donor's characteristic and apheresis instruments in China.
Platelet yield was associated with donor's characteristic and property of apheresis instruments. Here, we have analyzed the relationship of platelet yield, physiologic parameters of donors for different apheresis instruments in China. Data were consecutively retrieved from plateletapheresis donors during March 1, 2007 and March 1, 2012. Three different apheresis instruments MCS+, Amicus, Trima system were used for plateletapheresis and defined as group 1, 2 and 3 respectively. Totally 77,091 Plateletapheresis donations were performed in this study. 17 donations were finally aborted because of vasovagal reaction with syncope. 5861, 37,036, 34,177 donations were performed in group 1, 2 and 3 respectively. Hct and platelet values before donations were similar, but platelet yield and collection rate were showed significantly difference (p<0.05) among the three groups. The values of platelet and Hct in the males before donations were higher than those in the females, and the platelet yield and collection rate were showed significantly difference between the male group and female group (p<0.05). The overall reaction rate was 1.56%. Most donors were chosen the group 2 (51.6%) for next donation, followed by group 3 (33%) and group 1 (15.4%). We concluded that the platelet yield and collection rate in the male group were higher than those in the female group and the efficiency of plateletapheresis was associated with the kind of apheresis instruments and donor's characteristic. These data will help to work out suitable apheresis protocol based on the Chinese donor's characteristic.


Nucleoside transport inhibitor, dipyridamole, induced myocardial protection following hemorrhagic shock in ex vivo perfused rat hearts.
Successful protection against post-resuscitation myocardial injury is not available for trauma patients. Whereas intensive improvement in resuscitation strategies reduce myocardial injury, death among trauma patients are among the highest in the world due to myocardial dysfunction and multiple organ failure. Dipyridamole is a nucleoside transport inhibitor. Recent studies have shown that elevation of serum adenosine caused by dipyridamole improve cardiac function. The purpose of the present study was to examine the myocardial protective effects of dipyridamole therapy following 1 h of hemorrhagic shock. Sprague-Dawley rats were used. The study consisted of three phases: Phase I to examine the direct effects of dipyridamole on myocardial function by perfusion of the isolated hearts with Krebs Henseleit buffer (KHB) + dipyridamole on the Langendorff apparatus. Phase II examined the protective effects of dipyridamole following 60 min of hemorrhagic shock (HS) by ex vivo treatment with dipyridimole 20 μg/L for 5 min followed by resuscitation with KHB for 55 min. Phase III: 60 min HS followed by in vivo treatment by injecting 1 ml of (20 μg/L) dipyridamole intra-arterially, and resuscitation for 30 min. Myocardial protection was assessed by measuring left ventricular generated pressure (LVGP) and end diastolic pressures (LVEDP). During ex vivo resuscitation, hearts from dipyridamole treated animals had significantly higher LVGP, and significantly lower LVEDP versus controls. Dipyridamole therapy produces protection against post-resuscitation myocardial injury in rats.


Island pedicle graft in stomal stenosis: a new technique.
Pinpoint obstructive stenosis of the urinary stoma was treated in 5 patients after ileal conduit urinary diversion and in 2 with cutaneous ureterostomy. All 7 patients underwent a single-stage stomal revision with the use of 1 or more island pedicle skin grafts to increase stomal diameter. In each instance the stomal opening was enlarged sufficiently to relieve obstruction and morbidity. During patient followup from 18 months to 7 years no revised stoma has required subsequent intubation nor has stenosis recurred.


Effect of fibronectin on the haemolytic activity of complement.
Sheep erythrocytes were coupled with trinitophenyl sulphonate, sensitized with anti-TNP (or-DNP) IgM monoclonal antibodies, and exposed to components of the classical pathway of complement activation. When human fibronectin (FN) was added after C1q, but before addition of C1r and C1s (subunits of the first complement component), inhibition of haemolytic activity was observed which was strictly dependent upon the dose of FN. When FN was added after addition of C1 (reconstituted from C1q, C1r and C1s), the haemolytic activity of complement was not affected by the presence of FN. These data suggest that FN binds on C1q by interfering with C1r and C1s fixation. In addition, FN was unable to displace the activated subcomponents (C1r and C1s) from their binding site on C1q. When using other systems (sheep erythrocytes sensitized with anti-Forssman IgM monoclonal antibodies), the quantity of FN required to inhibit complement haemolytic activity was greater than in the TNP system. In normal plasma, there is a 50-fold excess of FN compared to free C1q.


Sonoproduction of nanobiomaterials - A critical review.
Ultrasound (US) demonstrates remarkable potential in synthesising nanomaterials, particularly nanobiomaterials targeted towards biomedical applications. This review briefly introduces existing top-down and bottom-up approaches for nanomaterials synthesis and their corresponding synthesis mechanisms, followed by the expounding of US-driven nanomaterials synthesis. Subsequently, the pros and cons of sono-nanotechnology and its advances in the synthesis of nanobiomaterials are drawn based on recent works. US-synthesised nanobiomaterials have improved properties and performance over conventional synthesis methods and most essentially eliminate the need for harsh and expensive chemicals. The sonoproduction of different classes and types of nanobiomaterials such as metal and superparamagnetic nanoparticles (NPs), lipid- and carbohydrate-based NPs, protein microspheres, microgels and other nanocomposites are broadly categorised based on the physical and/or chemical effects induced by US. This review ends on a good note and recognises US-driven synthesis as a pragmatic solution to satisfy the growing demand for nanobiomaterials, nonetheless some technical challenges are highlighted.


Changing role of chemotherapy in treatment of head and neck cancer.
The role of chemotherapy in the management of head and neck cancer includes treatment for recurrent disease and as an adjunct to conventional therapy with radiation and/or surgery in the primary treatment program. The best single agents, methotrexate and cisplatin, used for recurrent disease give response rates of 20 to 50 percent but of short duration. Results may be improved with combination chemotherapy, but often with increased toxicity. Prognostic factors that influence response are discussed. A newer role of chemotherapy in this disease is in the initial treatment program. Pretreatment chemotherapy can debulk these lesions prior to surgery and/or irradiation in up to 80 percent of patients. Controlled trials are in progress to determine the effect on cure rates. Chemotherapy utilized during radiotherapy has resulted in survival benefit in several studies. Post-treatment adjuvant chemotherapy still needs to be evaluated. The potential advantages and disadvantages of chemotherapy used in the initial treatment are discussed. Major strides have been made in the last decade in the treatment of head and neck cancer, and chemotherapy is assuming an increasingly important role.


The influence of the lordotic projection on the interpretation of the chest radiograph.
The advantages of the lordotic projection, particularly in elucidating suspected pathology at the lung apex, are well known. However, the distortion and artefact of the images of thoracic structures produced by this projection can lead to diagnostic errors. In order to determine the differences in the images produced we compared 14 pairs of lordotic and standard chest radiographs, taken within 24 h of each other, in the same patients. The main artefacts seen in the lordotic views were apparent elevation of the diaphragm, poor visualisation of the lung bases, loss of definition of the aortic knuckle, and apparent widening of the superior mediastinum. These artefacts were greatly exaggerated when lordosis coexisted with pathology, or technical factors such as patient rotation or inadequate respiration. Caution should be exercised to avoid misinterpretation of lordotic films.


Activities of (Poly)phenolic Antioxidants and Other Natural Autophagy Modulators in the Treatment of Sanfilippo Disease: Remarkable Efficacy of Resveratrol in Cellular and Animal Models.
Sanfilippo disease, caused by mutations in the genes encoding heparan sulfate (HS) (a glycosaminoglycan; GAG) degradation enzymes, is a mucopolysaccharidosis (MPS), which is also known as MPS type III, and is characterized by subtypes A, B, C, and D, depending on identity of the dysfunctional enzyme. The lack of activity or low residual activity of an HS-degrading enzyme leads to excess HS in the cells, impairing the functions of different types of cells, including neurons. The disease usually leads to serious psychomotor dysfunction and death before adulthood. In this work, we show that the use of molecules known as dietary (poly)phenolic antioxidants and other natural compounds known as autophagy activators (genistein, capsaicin, curcumin, resveratrol, trehalose, and calcitriol) leads to accelerated degradation of accumulated HS in the fibroblasts of all subtypes of MPS III. Both the cytotoxicity tests we performed and the available literature data indicated that the use of selected autophagy inducers was safe. Since it showed the highest effectivity in cellular models, resveratrol efficacy was tested in experiments with a mouse model of MPS IIIB. Urinary GAG levels were normalized in MPS IIIB mice treated with 50 mg/kg/day resveratrol for 12 weeks or longer. Behavioral tests indicated complete correction of hyperactivity and anxiety in these animals. Biochemical analyses indicated that administration of resveratrol caused autophagy stimulation through an mTOR-independent pathway in the brains and livers of the MPS IIIB mice. These results indicate the potential use of resveratrol (and possibly other autophagy stimulators) in the treatment of Sanfilippo disease.


Loss of neurons in the red nucleus after spinal cord transection.
Red nucleus neurons, particularly those of the caudal one-half of the nucleus, die or severely atrophy following complete spinal cord transection at T9. The size of residual horseradish peroxidase-labeled cells was smaller at 10 and 15 weeks, but those survivors which could be labeled at 25 weeks were normal in size. Hematoxylin and eosin-stained sections of the red nucleus at 52 weeks postoperative showed loss of cells from all size groups.


Altering the length-tension relationship with eccentric exercise : implications for performance and injury.
The effects of eccentric exercise on muscle injury prevention and athletic performance are emerging areas of interest to researchers. Of particular interest are the adaptations that occur after a single bout, or multiple bouts of eccentric exercise. It has been established that after certain types of eccentric exercise, the optimum length of tension development in muscle can be shifted to longer muscle lengths. Altering the length-tension relationship can have a profound influence on human movements. It is thought that the length-tension relationship is influenced by the structural makeup of muscle. However, the mechanism responsible for the shift in optimum length is not readily agreed upon. Despite the conflict, several studies have reported a shift in optimum length after eccentric exercise. Unfortunately, very few of these studies have been randomised, controlled training studies, and the duration of the shift has not yet been established. Nonetheless, this adaptation may result in greater structural stability at longer muscle lengths and consequently may have interesting implications for injury prevention and athletic performance. Both contentions remain relatively unexplored and provide the focus of this review.


Physiological changes associated with downsizing of personnel and reorganisation in the health care sector.
The objective of this study was to assess potential physiological changes associated with downsizing/reorganisation in the health care sector. The personnel reductions (1995-1997) in the studied regional hospital corresponded to one fifth of the personnel. In a longitudinal study, female personnel had blood sampled twice (8 a.m. and 4 p.m.) during a working day in 1997 (in connection with the last completed round of personnel redundancies) and 1 year later in 1998. The participants were 31 women (82% of those initially sampled ); there were 14 registered nurses, 11 assistant nurses and 6 medical secretaries. No additional drop outs took place during follow-up. Outcome variables were changes in the difference in serum cortisol levels between the morning and afternoon and in serum/plasma concentrations of immunoglobulin G (IgG), oestradiol, dehydroepiandrosterone sulphate (DHEAS), prolactin and apolipoproteins AI and B. Significantly decreased serum/plasma concentrations of IgG (p < 0.001), apolipoprotein AI (p < 0.001) and oestradiol (p < 0.001) were found. The difference between morning and afternoon serum cortisol decreased, with a change at the significance level of p = 0.05. No significant changes were observed regarding prolactin, DHEAS and apolipoprotein B. These results could be an indication that protective and anabolic functions had suffered in these remaining 'ageing' female work groups. The circadian cortisol rhythm was possibly flattened, which could be a sign of physiological dysfunction associated with the long-lasting adaptation process. These conclusions are tentative, given the small size of the sample and the lack of a control group. However, the findings point to the significance of studies of physiological changes possibly associated with restructuring of the health care sector.


Inhibition of protein phosphatases activates P4 promoter of the human insulin-like growth factor II gene through the specific promoter element.
To understand the transcriptional regulation of the human insulin-like growth factor II (IGF-II) gene, we examined the effects of okadaic acid, a potent in vitro inhibitor of protein phosphatases, on the activation of human IGF-II gene expression. Treatment of A-549 human lung adenocarcinoma cells with okadaic acid increased expression of the IGF-II mRNAs. Since the 4.8-kb mRNA is transcribed under the control of human IGF-II P4 promoter, we examined the P4 promoter element responsible for the okadaic acid-mediated transcriptional activation. Transfection of IGF-II P4 promoter-chloramphenicol acetyltransferase constructs demonstrated that the effects of okadaic acid on the induction of IGF-II gene expression are mediated through multiple promoter elements, including an Egr-1 consensus element. We have also shown that okadaic acid induced the expression of the transcription factor Egr-1. Moreover, by using a GAL4-Egr-1 fusion protein, we have directly demonstrated that okadaic acid positively regulates Egr-1 transcriptional activity in vivo. These results indicate that protein phosphatases play an important role in the transcriptional regulation of the IGF-II.


Connections of the mesencephalic locomotor region (MLR) II. Afferents and efferents.
Injections of a tritiated amino acid-fluorescent dye mixture were made unilaterally into the area of the mesencephalic locomotor region (MLR). After allowing for retrograde and anterograde transport, the same site was electrically stimulated to induce locomotion on a treadmill following a precollicular-postmamillary transection. The tritiated amino acid transported anterogradely primarily was found autoradiographically to descend in the area of Probst's tract and to ascend to the centremedian nucleus (CM) of the thalamus. Neurons labeled retrogradely by the fluorescent dye in the same injection-stimulation site were observed in the substantia nigra, entopeduncular nucleus, sub- and hypothalamus and amygdala. In subsequent experiments, injections of fluorescent tracers were made into the area of Probst's tract and CM. Neurons in the mesencephalic trigeminal root, cuneiform nucleus, nucleus tegmenti pedunculopontinus (NTPP), dorsal locus coeruleus and lateral central gray were labeled from Probst's tract injections. Neurons in medial and lateral central gray, as well as NTPP, were labeled from CM injections.


Youth Access to Tobacco Products in the United States, 2016-2018.
In 2018, approximately 4.9 million US middle and high school students reported past 30-day use of any tobacco product. This study describes how and where youth obtained tobacco products and whether refusal of sale occurred during 2016-2018. Data from 3 annual waves (2016-2018) of the National Youth Tobacco Survey, a school-based survey of US youth in grades 6-12, were analyzed among current (past 30-day) tobacco product users aged 9 to 17 years. During 2016-2018, youth tobacco product users most commonly obtained tobacco products from social sources. Although the percentage of users who reported buying tobacco products significantly decreased from 2016 to 2018 (2016: 15.6%; 2018: 11.4%), no significant differences in the prevalence of being refused sale were observed (2016: 24.7%; 2018: 25.5%). Whereas the number of youth users who report buying tobacco products has declined, sales of tobacco products to youth remain a public health concern, as only one in 4 youth who attempted to buy were refused sale in 2018. Monitoring youth tobacco product purchases, retailer compliance check inspections, and retailer penalties for sales to minors remain important for reducing youth access at retail sources.


Eu(III) transfer in single N,N,N',N'-tetraoctyldiglycolamide-impregnated polymer-coated silica particle using fluorescence microspectroscopy: transfer mechanism and effect of polymer crosslinking degree.
A microcapillary manipulation system combined with fluorescence microspectroscopy enabled us to analyze mass transfer in a single particle. In this study, we revealed the Eu(III) distribution in a single diglycolamide-derivative extractant (TODGA)-impregnated polymer-coated silica particle. The reaction of Eu(III) with two TODGA molecules in the polymer layer was the rate-limiting process, which was revealed by the relationship between the rate constants (k1 and k-1) and concentrations of Eu(III) and HNO3. The decrease in the crosslinking degree of the polymer layer caused an increase in only k-1. This indicates that hydrophilic environments at lower crosslinking degrees enhance the stability of the charged Eu(III) species such as Eu3+, Eu(NO3)2+, and Eu(NO3)2+.


When patients get stuck: A systematic literature review on throughput barriers in hospital-wide patient processes.
Hospital productivity is of great importance to policymakers, and previous research demonstrates that improved hospital productivity can be achieved by directing more focus towards patient throughput at healthcare organizations. There is also a growing body of literature on patient throughput barriers hampering the flow of patients. These projects rarely, however, encompass complete hospitals. Therefore, this paper provides a systematic literature review on hospital-wide patient process throughput barriers by consolidating the substantial body of studies from single settings into a hospital-wide perspective. Our review yielded a total of 2207 articles, of which 92 were finally selected for analysis. The results reveal long lead times, inefficient capacity coordination and inefficient patient process transfer as the main barriers at hospitals. These are caused by inadequate staffing, lack of standards and routines, insufficient operational planning and a lack in IT functions. As such, this review provides new perspectives on whether the root causes of inefficient hospital patient throughput are related to resource insufficiency or inefficient work methods. Finally, this study develops a new hospital-wide framework to be used by policymakers and healthcare managers when deciding what improvement strategies to follow to increase patient throughput at hospitals.


DNA image cytometry ploidy analysis technique improves the detection rate of pleural effusion cytology.
To explore the clinical diagnostic value of DNA image cytometry (DNA-ICM) ploidy analysis in malignant pleural effusion cancer screening, this study analyzed the effect of exfoliated cell smears (ECSs), cell blocks (CBs), and immunochemistry. A total of 830 cases of pleural effusion were considered for the DNA-ICM ploidy analysis. The ECSs were centrifuged, the CBs were formed, and the DNA-ICM ploidy analysis was carried out in the diagnosis of malignant pleural effusion. Immunochemistry and biopsy was applied to differentiate between benign and malignant pleural effusion and to determine the source of the latter. The sensitivity and specificity differences between the three methods alone and in combination were compared. The sensitivity of the DNA-ICM, ECS, and CB methods was 96.28%, 94.93%, and 95.95%, respectively, and the specificity of each method was 86.52%, 87.08%, and 86.14%, respectively. The sensitivity and specificity of the combined diagnosis method were 99.32% and 75.09%, respectively. Among the 22 cases diagnosed as positive in the DNA-ICM ploidy analysis but negative in the ECS and CB analyses, four cases were diagnosed as positive by comprehensive clinical diagnosis. The sensitivity and specificity of DNA-ICM ploidy analysis are high; the positive detection rate of pleural fluid cytology is effectively increased, and the missed detection rate of cell pathologies is effectively reduced. The combination of the three methods significantly improves the specificity and sensitivity of the diagnosis of malignant pleural effusion, and immunochemistry with CBs can be used to accurately analyze the primary tumor site.


DBP exposure induces thyroid inflammatory impairment through activating AKT/NF-κB/NLRP3 signaling.
Previous studies exhibited reproductive and neurodevelopmental toxicity in rats exposed to Di-n-butyl phthalate (DBP). However, the effects of DBP exposure on the other endocrine organ are still unclear. This study aimed to assess the impact of DBP exposure on the thyroid of male rats and the associated mechanisms. Here, rats were respectively treated with DBP at 0 (control), 50 (low dose), 250 (medium dose), or 500 (high dose) mg/kg/day dissolved in 1 ml quantity of corn oil by intragastrical administration for two weeks. The results demonstrated that the proliferation and inflammatory response changes were significantly different compared to the control. In vivo DBP is mainly converted to mono-n-butyl phthalate (MBP), an active form producing untoward reactions of DBP exposure. Therefore, for in vitro experiments, we treated the thyroid follicular epithelial cell line (Nthy-ori 3-1) in a temporal gradient using 1 mM MBP. Further in vitro studies showed that MBP exposure upregulated tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), as well as interleukin-1β (IL-1β) by activating AKT/NF-κB/NLRP3 signaling. Meanwhile, we detected that Pellino2 (Peli2) played an essential role in promoting the activation of NLRP3 inflammasome. Briefly speaking, this study confirmed that DBP exposure caused impaired thyroid structure and thyroid inflammation in male rats, which offered new views into the harm of DBP exposure on the endocrine organ.


Role of Health Insurance Status in Interfacility Transfers of Patients With ST-Elevation Myocardial Infarction.
Lack of health insurance is associated with interfacility transfer from emergency departments for several nonemergent conditions, but its association with transfers for ST-elevation myocardial infarction (STEMI), which requires timely definitive care for optimal outcomes, is unknown. Our objective was to determine whether insurance status is a predictor of interfacility transfer for emergency department visits with STEMI. We analyzed data from the 2006 to 2011 Nationwide Emergency Department Sample examining all emergency department visits for patients age 18 years and older with a diagnosis of STEMI and a disposition of interfacility transfer or hospitalization at the same institution. For emergency department visits with STEMI, our multivariate logistic regression model included emergency department disposition status (interfacility transfer vs hospitalization at the same institution) as the primary outcome, and insurance status (none vs any [including Medicare, Medicaid, and private insurance]) as the primary exposure. We found that among 1,377,827 emergency department STEMI visits, including 249,294 (18.1%) transfers, patients without health insurance (adjusted odds ratio 1.6, 95% CI 1.5 to 1.7) were more likely to be transferred than those with insurance. Lack of health insurance status was also an independent risk factor for transfer compared with each subcategory of health insurance, including Medicare, Medicaid, and private insurance. In conclusion, among patients presenting to United States emergency departments with STEMI, lack of insurance was an independent predictor of interfacility transfer. In conclusion, because interfacility transfer is associated with longer delays to definitive STEMI therapy than treatment at the same facility, lack of health insurance may lead to important health disparities among patients with STEMI.


Core-Shell Nanostructured Drug Delivery Platform Based on Biocompatible Metal-Organic Framework-Ligated Polyethyleneimine for Targeted Hepatocellular Carcinoma Therapy.
Multifunctional nanosized metal-organic frameworks (NMOFs) have advanced rapidly over the past decade to develop drug delivery systems (DDSs). These material systems still lack precise and selective cellular targeting, as well as the fast release of the quantity of drugs that are simply adsorbed within and on the external surface of nanocarriers, which hinders their application in the drug delivery. Herein, we designed a biocompatible Zr-based NMOF with an engineered core and the hepatic tumor-targeting ligand, glycyrrhetinic acid grafted to polyethyleneimine (PEI) as the shell. The improved core-shell serves as a superior nanoplatform for efficient controlled and active delivery of the anticancer drug doxorubicin (DOX) against hepatic cancer cells (HepG2 cells). In addition to their high loading capacity of 23%, the developed nanostructure DOX@NMOF-PEI-GA showed an acidic pH-stimulated response and extended the drug release time to 9 days as well as enhanced the selectivity toward the tumor cells. Interestingly, the DOX-free nanostructures showed a minimal toxic effect on both normal human skin fibroblast (HSF) and hepatic cancer cell line (HepG2), but the DOX-loaded nanostructures exhibited a superior killing effect toward the hepatic tumor, thus opening the way for the active drug delivery and achieving efficient cancer therapy applications.


Tracing the origin of an imported HIV-1 sub-subtype A6 strain first identified in Zhejiang Province, China.
Human migration and mobility have been identified as key drivers of HIV dissemination among nations, which increases the problem of genetic diversity. Here, we report the near full-length genome of HIV-1 A6 identified in a female patient in the remote mountain area of Lishui, Zhejiang Province, which is the first time A6 has been reported in China. The near full-length genome was amplified with two large amplicons of 5.5 kb and 3.7 kb, and then target PCR products were sequenced by Sanger sequencing. The A6 strain was confirmed by the Basic Local Alignment Search Tool (BLAST) and a maximum-likelihood (ML) phylogenetic tree. The time to the most recent common ancestor (tMRCA) was inferred to be 2004 (95% HPD interval: 2003-2006). The sequence harbored the L74I mutation, which is a key characteristic genetic marker of A6. Combining the above evidence with epidemiological investigations, this A6 strain was determined to be from Ukraine, which was supported by phylogenetic analysis. This study identified a foreign imported strain, indicating a trend of increasing complication in the HIV-1 epidemic in Zhejiang, China.


Allosteric HIV Integrase Inhibitors Promote Formation of Inactive Branched Polymers via Homomeric Carboxy-Terminal Domain Interactions.
The major effect of allosteric HIV integrase (IN) inhibitors (ALLINIs) is observed during virion maturation, where ALLINI treatment interrupts IN-RNA interactions via drug-induced IN aggregation, leading to the formation of aberrant virions. To understand the structural changes that accompany drug-induced aggregation, we determined the soft matter properties of ALLINI-induced IN aggregates. Using small-angle neutron scattering, SEM, and rheology, we have discovered that the higher-order aggregates induced by ALLINIs have the characteristics of weak three-dimensional gels with a fractal-like character. Their formation is inhibited by the host factor LEDGF/p75, as well as ex vivo resistance substitutions. Mutagenesis and biophysical analyses reveal that homomeric carboxy-terminal domain interactions are required to achieve the branched-polymer nature of the ALLINI-induced aggregates. These studies provide key insight into the mechanisms of ALLINI action and resistance in the context of the crowded virion environment where ALLINIs exert their effect.


Experimental study of cerebrospinal fluid tumor necrosis factor-alpha release in penicillin- and cephalosporin-resistant pneumococcal meningitis treated with different antibiotic schedules.
To measure the inflammatory response in terms of tumor necrosis factor-alpha (TNF-α) levels in cerebrospinal fluid (CSF), using bacteriolytic versus nonbacteriolytic antibiotic therapy and adjunctive treatment with dexamethasone in an experimental rabbit model of pneumococcal meningitis. In a rabbit model of pneumococcal meningitis, we tested CSF TNF-α levels in several samples from rabbits infected with the HUB 2349 strain and treated with ceftriaxone 100 mg/kg/d, ceftriaxone plus vancomycin 30 mg/kg/d, or daptomycin at 15 mg/kg or 25 mg/kg. Daptomycin schedules were compared with the same doses in combination with dexamethasone at 0.125 mg/kg every 12 hours over a 26-hour period. The ceftriaxone group had the highest levels of TNF-α. TNF-α levels were significantly higher after ceftriaxone administration than in both daptomycin groups. The high-dose daptomycin group presented the lowest inflammatory levels in CSF samples. Adjunctive treatment with dexamethasone in this group modulated the inflammatory response, bringing down CSF TNF-α levels. CSF TNF-α levels were significantly lower in rabbits treated with daptomycin than in rabbits treated with ceftriaxone. Daptomycin avoided the inflammatory peak after administration observed in ceftriaxone-treated rabbits. The use of daptomycin plus dexamethasone achieved a significantly larger reduction in CSF TNF-α levels.


Identifying the Assembly Configuration and Fluorescence Spectra of Nanoscale Zinc-Tetraphenylporphyrin Aggregates with Scanning Tunneling Microscopy.
ZnTPP (Zinc-Tetraphenylporphyrin) is one of the most common nanostructured materials, having high stability and excellent optoelectronic properties. In this paper, the fluorescence features of self-assembled ZnTPP monomers and aggregates on Au(111) surface are investigated in detail on the nanometer scale with scanning tunneling microscopy (STM). The formation of ZnTPP dimers is found in thick layers of a layer-by-layer molecular assembly on Au substrate with its specific molecular arrangement well characterized. Tip-induced luminescence shows a red shift from tilted dimers comparing with the behavior from monomers, which can be attributed to the change of vibrational states due to the intermolecular interaction and the increasing dielectric effect. The nanoscale configuration dependence of electroluminescence is demonstrated to provide a powerful tool aiding the design of functional molecular photoelectric devices.


Rural/urban differences in rates and predictors of intimate partner violence and abuse screening among pregnant and postpartum United States residents.
To describe rates and predictors of perinatal intimate partner violence (IPV) and rates and predictors of not being screened for abuse among rural and urban IPV victims who gave birth. This analysis utilized 2016-2020 Pregnancy Risk Assessment Monitoring System (PRAMS) data from 45 states and three jurisdictions. This is a retrospective, cross-sectional study using multistate survey data. This analysis included 201,413 survey respondents who gave birth in 2016-2020 (n = 42,193 rural and 159,220 urban respondents). We used survey-weighted multivariable logistic regression models, stratified by rural/urban residence, to estimate adjusted predicted probabilities and 95% confidence intervals (CIs) for two outcomes: (1) self-reported experiences of IPV (physical violence by a current or former intimate partner) and (2) not receiving abuse screening at health care visits before, during, or after pregnancy. Rural residents had a higher prevalence of perinatal IPV (4.6%) than urban residents (3.2%). Rural respondents who were Medicaid beneficiaries, 18-35 years old, non-Hispanic white, Hispanic (English-speaking), or American Indian/Alaska Native had significantly higher predicted probabilities of experiencing perinatal IPV compared with their urban counterparts. Among respondents who experienced perinatal IPV, predicted probabilities of not receiving abuse screening were 21.3% for rural and 16.5% for urban residents. Predicted probabilities of not being screened for abuse were elevated for rural IPV victims who were Medicaid beneficiaries, 18-24 years old, or unmarried, compared to urban IPV victims with those same characteristics. IPV is more common among rural birthing people, and rural IPV victims are at higher risk of not being screened for abuse compared with their urban peers. IPV prevention and support interventions are needed in rural communities and should focus on universal abuse screening during health care visits and targeted support for those at greatest risk of perinatal IPV.


Genes associated with addiction: alcoholism, opiate, and cocaine addiction.
Drug addiction is a complex disorder that has a large spectrum of causes. Vulnerability to addiction has been shown in twin studies to have a robust genetic component. This genetic basis for addiction has general and specific components for each drug abused. Although many genes have been implicated in drug addiction, only a handful have either been replicated to have an association or to have an identified functional mechanism related to specific effects of abused drugs. A few selected genetic variants that currently look promising for the study of alcohol, opiate, and cocaine addiction are discussed in this article.


Der f 16: a novel gelsolin-related molecule identified as an allergen from the house dust mite, Dermatophagoides farinae.
Allergen from the house dust mite (Dermatophagoides sp.) is a major trigger factor of allergic disorders, and its characterization is crucial for the development of specific diagnosis or immunotherapy. Here we report the identification of a novel dust mite (Dermatophagoides farinae) antigen whose primary structure belongs to the gelsolin family, a group of actin cytoskeleton-regulatory proteins. Isolated mite cDNA, termed Der f 16, encodes 480 amino acids comprising a four-repeated gelsolin-like segmental structure, which is not seen in conventional gelsolin family members. Enzyme immunoassay indicated that recombinant Der f 16 protein, prepared using an Escherichia coli expression system, bound IgE from mite-allergic patients at 47% (8/17) frequency. This is the first evidence that the gelsolin family represents a new class of allergen recognizable by atopic patient IgE.


Racial disparities in new-onset diabetes mellitus in prostate cancer patients on androgen deprivation therapy: a retrospective analysis of TriNetX data.
Prostate cancer (PCa) is the most common cancer in men in the US and androgen deprivation therapy (ADT) is the most frequently used systemic therapy for PCa. Data suggest that ADT is associated with an increased risk of new-onset diabetes mellitus (NODM) and cardiovascular complications. As the incidence and mortality of PCa are highest among the African American (AA) population, it is important to evaluate the difference in the incidence of NODM and ischemic heart disease (IHD) between AA men compared to Caucasian men. This is a retrospective cohort study utilizing the TriNetX database to assess NODM and IHD risk, risk difference, and risk ratio (RR) after recent ADT initiation in an AA cohort and a Caucasian cohort of patients with PCa. Propensity score matching (PSM) was performed by age, BMI, and confounding comorbidities. After matching, the cohort included 1159 AA patients and 843 Caucasian patients with NODM after ADT initiation. The IHD cohort included 1269 AA patients and 1248 Caucasian patients. The risk of incidence of NODM is higher among AA men at 11.6% risk compared to Caucasian men at 7.4%. The risk difference is 4.1% (95% CI = 3.4, 4.9) p = 0.000. The RR is 1.56 (95% CI = 1.43, 1.70). In contrast, risk difference and risk ratio of IHD was not significant between AA and Caucasian groups. ADT exposure increases the risk of NODM in men with PCa, especially among AA men compared with Caucasian men. Men receiving ADT should be monitored routinely for signs and symptoms of metabolic syndrome and diabetes. Targeted close monitoring of AA men on ADT would be critical to prevent and treat metabolic complications with potential of reducing disparities in PCa morbidity.


Which renal lacerations will heal satisfactorily with nonsurgical management?
If there was a correlation between the type of renal laceration and its healing, and if radiologic evaluation on admission could accurately diagnose the type of renal laceration present, then surgical intervention could be reserved for those renal lacerations that will not heal satisfactorily by themselves. We reviewed the outcome of initially conservative or immediate operative treatment of renal laceration in 122 patients. Thirty-six patients were managed initially without operation. All fifteen cortical lacerations and all five deep lacerations that created only a small parenchymal defect healed themselves, with 4 of the 16 patients available for follow-up having hypertension. In contrast, six deep lacerations that caused large parenchymal defects, six disrupted poles or segments, and four split kidneys did not have satisfactory healing with conservative management, necessitating delayed renal surgery, or causing hypertension or both. Because computed tomography on admission can accurately diagnose the site and extent of a renal laceration, it should be possible to decide early which patients truly will benefit from conservative management.


Lower HDAC6 mRNA expression and promoter hypomethylation are associated with RA susceptibility.
Recent studies showed that Histone deacetylases 6 (HDAC6) inhibitors could improve arthritis in rheumatoid arthritis (RA) rodent models, whereas lower HDAC6 expression was observed in RA patients' synovial fibroblasts, raising the concerns to use HDAC6 inhibitors to treat RA patients. In the present study, we investigated the involvement of HDAC6 mRNA expression and promoter methylation in RA. The DNA and RNAs were extracted from the peripheral blood mononuclear cells (PBMCs) from 138 RA patients and 102 healthy controls. The pyrosequencing technique was used for promoter methylation analysis. The quantitative real-time polymerase chain reaction was used to determine the HDAC6 mRNA expression. The patients' clinical characteristics and disease biomarkers were recorded when blood sampling. The HDAC6 mRNA expression was lower in the RA patients than controls (p = 0.001). The RA patients had significant hypomethylation of the HDAC6 promoter (p < 0.001). The HDAC6 promoter was hypo-methylated in the -229, -225, -144, and -142 CpG sites in RA patients (p < 0.05). Unexpectedly, promoter methylation and mRNA expression of the HDAC6 gene were positively associated (p < 0.001). The HDAC6 mRNA expression and promoter methylation status were associated with the risk of RA (p = 0.006 and 0.002, respectively). The inflammatory cytokines, TNF-α and IL-6, were significantly increased after HDAC6 knockdown in PMA-stimulated THP1 cells and SW982 cells (p < 0.05). The HDAC6 mRNA expression and promoter methylation were lower in RA patients. Both HDAC6 mRNA expression level and promoter hypomethylation were associated the susceptibility of RA. HDAC6 inhibitors seem not proper for RA patients' treatment.


[Distribution of the antigen of hepatitis B virus in liver tissue in healthy carriers and in patients with chronic active and acute hepatitis].
We have studied 120 cases of B hepatitis. Sixty were healthy carriers of B virus, 40 had chronic active hepatitis (CAH) and 20 acute hepatitis (AH). The AgsHBV distribution was made in liver tissue by immunoperoxidase technic. In 73% of patients with CAH the AgsHBV was found around portal tracts. In contrast in patients with AH the AgsHBV was seen around central vein. Healthy carriers showed an disseminated pattern. All healthy carrier had AgSHBV in liver, in contrast only 65% of patients with CAH and 20% with AH exhibited AgSHBV in liver biopsy.


The value of DNA storage and pedigree analysis in rare diseases: a 17-year-old boy with X-linked lymphoproliferative disease (XLP) caused by a de novo SH2D1A mutation.
We present a case of a fatal Epstein-Barr infection in a 17-year-old male patient suspected to be caused by X-linked lymphoproliferative disease. At the time of hospitalization, DNA diagnostics was not available. The suspected diagnosis was confirmed several years later when a SH2D1A missense mutation was identified in stored patient DNA. Extended pedigree analysis showed that this mutation occurred de novo in his mother. In addition, we provide a summary of the currently listed SH2D1A mutations. This case report underlines the importance of DNA storage, pedigree analysis, and multidisciplinary care in patients with rare diseases and their families.


Removal of organophosphate pesticides from wastewater by supercritical carbon dioxide extraction.
Organophosphate pesticides including fenitrothion chlorpyrifos, diazinon, methamidophos, edifenphos, mevinphos, fenthion, and acephate present in agro-wastewater can be effectively removed by supercritical carbon dioxide (SC-CO2) extraction. Near quantitative removal of the pesticides from the aqueous solution can be achieved by SC-CO2 at 90 degrees C and 325 atm for 20 min of static extraction followed by 40 min of dynamic extraction. The extracted pesticides were collected in a small amount of Fenton's solution. The pesticides in Fenton's solution were degraded completely within an hour after the collection. A combination of SC-CO2 extraction and subsequent degradation by Fenton's reagent may provide an alternative water purification strategy for treating organophosphate pesticides in agro-wastewater.


Allergoprints in horse allergic children.
In order to determine the allergenic activity of five purified horse allergens, 22 children allergic to horses according to history, skin test, and leukocyte histamine release were evaluated. Washed leukocytes from all patients were tested for allergen-induced histamine release utilizing four epidermal horse allergens (Ags 6, 9, 11, and 15) and horse serum albumin. Crossed radioimmunoelectrophoresis was carried out with a standard horse dander extract and serum from each patient. The results showed considerable variation in the individual allergoprints. Ag 11 had the highest mean allergenic activity. Sensitivity to horse serum albumin was demonstrated three times. Our data show that the amount of serum IgE antibodies bound by horse allergens correlates significantly with the capacity of the allergens to induce histamine release from washed leukocytes.


BMPR2 germline mutation in chronic thromboembolic pulmonary hypertension.
Heterozygous germline mutations of the bone morphogenetic protein type II receptor (BMPR2) gene BMPR2 are the most important predisposing factors for heritable pulmonary arterial hypertension. BMPR2 mutation was occasionally reported in pulmonary veno-occlusive disease, appetite suppressant-related pulmonary arterial hypertension (PAH), and PAH with congenital heart disease. In this study we identified a missense mutation (c.2296A > G) located in BMPR2 exon 12 in a patient with chronic thromboembolic pulmonary hypertension (CTEPH). It is the first report of a BMPR2 mutation in CTEPH. Our study provides innovative insight into etiology of CTEPH. The genetic predisposing factor is an important component in the process of this CTEPH patient.


[Evidence-based therapy of systemic sclerosis].
For the treatment of different forms of systemic sclerosis (SSc), drugs play a predominant role. Depending on disease activity as well as type and severity of cutaneous, vascular and internal organ manifestations, different systemic (antiinflammatory, immunosuppressive, antifibrotic) or organ-specific therapies are used. The scientific basis of most treatment modalities is insufficient and incomplete. There is sufficient evidence for an antiinflammatory and antiproliferative efficacy of glucocorticosteroids, methotrexate, cyclophosphamide and cyclosporine A in the treatment of diffuse cutaneous systemic sclerosis. Vasoactive therapies play an important role in treating Raynaud's phenomenon (nifedipine or other dihydropyridines, prostaglandin analogs, losartan, prazosine), and arterial (ACE blockers, AT-1 antagonists) or pulmonary (epoprostenol) hypertension. Cyclophosphamide is effective in fibrosing alveolitis, prokinetic substances (metoclopramid, domperidone) in gastroesophageal dysmotility or octreotide in intestinal pseudoobstruction. Physical therapies (e.g., massage) are poorly studied. In particular cases, surgical measures (e.g., removal of calcifications) are necessary.


[Measuring the subjective visual vertical using a portable system: a comparison with the standard darkroom method].
Assessing otolithic functions in the case of vertigo, although significant, is challenging from a practical point of view. A tilt of the subjective visual vertical (SVV) is a very sensitive sign of vestibular tonus imbalance in the roll plane. The standard method, a light bar in the dark, requires expensive, stationary equipment. However, portable equipment has been developed. The patient, who is in complete darkness afforded by a cover, sits in front of a monitor that can be seen by him and the examiner. Results obtained with this system were validated and compared with the standard application. Measurements were taken in 100 unselected, consecutive patients suffering from dizziness treated at the Baumrain Klinik, Bad Berleburg as well as in 26 healthy volunteers. All were examined and diagnosed by an ENT physician. Measurements in all participants were taken first with the standard procedure (equipment Vertitest) followed by the portable procedure (Vertistar equipment). In each case the deviation of the absolute from the true vertical was measured and the mean differences between the two procedures calculated. These were then analyzed using a paired t-test with the help of the SPSS system. Comparative measurements in the dizziness group (n = 100), t(25) = 0.868, p = 0.394 and in the healthy control group (n = 26), t(99) = -0.192, p = 0.848 showed no significant differences in the distribution of SVV values while using the stationary or the portable version. Inter-test reliability was significantly positive (r = 0.852; p < 0.01, n = 126). The portable method for measuring SVV is practical, flexible and cost-effective and demonstrates the same diagnostic accuracy as the stationary method.


Nanoscale assembly line composed of dual DNA-machines enabling sensitive microRNA detection using upconversion nanoparticles probes.
DNA machines are smart artificial devices that perform well-organized DNA hybridization reactions or nanoscale mechanical movements. Herein, a nanoscale assembly line composing of dual DNA machines is meticulously designed by coupling a catalytic hairpin assembly (CHA)-based machine with a 3D DNA walker machine. Equipped with upconversion nanoparticles (UCNPs) as signal tags, the dual DNA machines-based assembly line (DDMAL) can efficiently amplify the fluorescent signal of target recognition event, enabling sensitive detection of microRNA (miRNA). In detail, once activated by target miRNA-21, the CHA machine is initiated to constantly produce a single-stranded DNA (named binding DNA) via the strand displacement reaction. The binding DNA as a trigger factor can initiate the DNA walker machine by linking a walking strand DNA with an anchor strand DNA immobilized on the surface of magnetic beads (MBs). The movement of walking strand on the surface of MBs is then driven by Mn2+-dependent DNAzyme formed through the hybridization of walking strand with a UCNPs-linked substrate strand. The DNAzyme-catalyzed cleavage of substrate strand is accompanied by the release of numerous UCNPs from MBs. By measuring the fluorescent signal of released UCNPs after the magnetic separation, target miRNA-21 can be detected by the DDMAL system in a linear range from 1.0 fM to 10 nM, with a limit of detection (LOD) of 0.62 fM (3σ). Moreover, the practicability of DDMAL system was demonstrated by using it to evaluate the expression levels of miRNA-21 in cell lines and assay miRNA-21 in human serum.


Evolution of increased complexity in a molecular machine.
Many cellular processes are carried out by molecular 'machines'-assemblies of multiple differentiated proteins that physically interact to execute biological functions. Despite much speculation, strong evidence of the mechanisms by which these assemblies evolved is lacking. Here we use ancestral gene resurrection and manipulative genetic experiments to determine how the complexity of an essential molecular machine--the hexameric transmembrane ring of the eukaryotic V-ATPase proton pump--increased hundreds of millions of years ago. We show that the ring of Fungi, which is composed of three paralogous proteins, evolved from a more ancient two-paralogue complex because of a gene duplication that was followed by loss in each daughter copy of specific interfaces by which it interacts with other ring proteins. These losses were complementary, so both copies became obligate components with restricted spatial roles in the complex. Reintroducing a single historical mutation from each paralogue lineage into the resurrected ancestral proteins is sufficient to recapitulate their asymmetric degeneration and trigger the requirement for the more elaborate three-component ring. Our experiments show that increased complexity in an essential molecular machine evolved because of simple, high-probability evolutionary processes, without the apparent evolution of novel functions. They point to a plausible mechanism for the evolution of complexity in other multi-paralogue protein complexes.


Hypoxia regulates adipose mesenchymal stem cells proliferation, migration, and nucleus pulposus-like differentiation by regulating endoplasmic reticulum stress via the HIF-1α pathway.
Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.


C-H Activation by an Iron-Nitrido Bis-Pocket Porphyrin Species.
High-valent iron-nitrido species are nitrogen analogues of iron-oxo species which are versatile reagents for C-H oxidation. Nonetheless, C-H activation by iron-nitrido species has been scarcely explored, as this is often hampered by their instability and short lifetime in solutions. Herein, the hydrogen atom transfer (HAT) reactivity of an Fe porphyrin nitrido species (2 c) toward C-H substrates was studied in solutions at room temperature, which was achieved by nanosecond laser flash photolysis (LFP) of its FeIII -azido precursor (1 c) supported by a bulky bis-pocket porphyrin ligand. C-H bonds with bond dissociation enthalpies (BDEs) of up to ≈84 kcal mol-1 could be activated, and the second-order rate constants (k2 ) are on the order of 102 -104 s-1 m-1 . The Fe-amido product formed after HAT could further release ammonia upon protonation.


Genistein increases estrogen receptor beta expression in prostate cancer via reducing its promoter methylation.
Genistein has protective effects against prostate cancer (PCa) but whether this protection involves an estrogen receptor (ER) β dependent mechanism has yet to be elucidated. ER-β has a tumor suppressor role in PCa and its levels decline with cancer progression which was linked to ER-β promoter hypermethylation. Genistein has been suggested to have demethylating activities in cancer. However, the ability of genistein to reverse ER-β promoter hypermethylation in PCa has not been studied. In addition, there are great discrepancies among studies that examined the effect of genistein on ER-β gene expression. Therefore, we sought to explore effects of genistein on ER-β promoter methylation as a mechanism of modulating ER-β expression using three PCa cell lines, LNCaP, LAPC-4 and PC-3. We also examined the role of ER-β in mediating the preventive action of genistein. Our data demonstrated that genistein at physiological ranges (0.5-10 μmol/L) reduced ER-β promoter methylation significantly with corresponding dose-dependent increases in ER-β expression in LNCaP and LAPC-4 but not in PC-3 cells, which could be attributed to the low basal levels of ER-β promoter methylation in PC-3 cell line. Genistein induced phosphorylation, nuclear translocation and transcriptional activity of ER-β in all three PCa cell lines. Inhibitory effects of genistein on LAPC-4 and PC-3 cell proliferation were diminished using a specific ER-β antagonist. In conclusion, genistein and ER-β act together to prevent PCa cell proliferation; genistein increases ER-β levels via reducing its promoter methylation and ER-β, in turn, mediates the preventive action of genistein.


Chitosan nanoparticles mitigate Alternaria leaf spot disease of chilli in nitric oxide dependent way.
The present study focuses on protection of emerging Alternaria leaf spot disease of chilli by application of chitosan nanoparticles (CNP). CNP was prepared by ionotropic gelation method and characterized. Antifungal potential of CNP was also checked against Alternaria alternata and its mechanisms were unraveled. Foliar application of CNP (0.001%) improved plant innate immunity in two chilli cultivars (one tolerant and one susceptible) by inducing the activities of different defense related enzymes along with total phenol and flavonoid. CNP application also induced callose deposition and reduced cell death in both the cultivar. Signaling molecule nitric oxide (NO) also augmented in CNP treated sets which were confirmed by both biochemical and microscopic data. In order to find out involvement of NO in CNP induced innate immunity in chilli cultivars, both NO surplus and NO depleted conditions were artificially created and defense responses were recorded. It was interesting to note that CNP mediated enhancement of defense responses in chilli plants was compromised in NO depleted condition. These results signify possible involvement of NO in CNP induced defense responses in chilli plants. It is evident from our results that CNP can be used to protect chilli plants against this fungal disease to develop a sustainable management strategy.


Mapping the DNA fragments produced by cleavage of EcoRI F fragment of adenovirus 2 with HaeIII, HpaII and AluI.
Hydrolysis of the EcoRI F fragment of the adenovirus 2 genome with HaeIII, HpaII and AluI restriction enzymes gives respectively 9, 11, and 11 fragments, the size of which ranges from 20 bp for the smallest HpaII k fragment to 585 for the largest AluI A fragment. The order of fragments was mainly deduced from partial hydrolysis analyses. The relative order of all restriction sites and the distance in nucleotides between them were obtained through secondary analyses of each restriction fragment by the two other enzymes. Position of the KpnI, HindIII, MboI and SmaI sites within the EcoRI F fragment were also reevaluated.


Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study.
The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy.


Effects of mouth rehabilitation with removable complete dentures on stimulus perception and the electromyographic activity of the orbicularis oris muscle.
Many elderly individuals are rehabilitated with removable complete dentures, which require an initial adaptation period for both oral perception and the perioral muscles. Studies assessing the changes in stimulus perception and the electromyographic (EMG) activity of the orbicularis oris muscle shortly after conventional complete denture insertion are lacking. The purpose of this clinical study was to evaluate the effect of mouth rehabilitation with removable complete dentures on stimulus perception and the EMG activity of the orbicularis oris muscle. This study was approved by the Human Research Ethics Committee of the Araçatuba Dental School (São Paulo State University). Fifteen participants who had worn their removable complete dentures for at least 5 years and needed rehabilitation with new prostheses were enrolled in the study. A perception questionnaire was applied, and surface EMG examinations of the orbicularis oris muscle during rest, suction of water with a straw, and pronunciation of the syllables /bah/, /mah/, /pah/, and the word 'Mississippi' were performed before (T0) and 30 (T1) and 100 (T2) days after insertion of the new prostheses. The data were analyzed with the Cochran Q test, McNemar test, 2-way repeated measures ANOVA, and honestly significant difference (HSD) Tukey test (α=.05). Significant improvement was reported in the perception questionnaire in terms of the oral discomfort sensation in the T2 period. EMG activity decreased during rest and suction after insertion of the new prostheses. A statistical difference between the upper and lower fascicles of the orbicularis oris muscle was detected, with a decrease of EMG activity between the T0 and T1 periods on the lower fascicle, except for when pronouncing the /pah/ syllable. Mouth rehabilitation with removable complete dentures decreased oral discomfort and, depending on the oral function, decreased or increased EMG activity of the orbicularis oris muscle. In addition, the lower fascicle was more active than the upper fascicle during rest and most functional activities.


Rural youths' understanding of gene x environmental contributors to heritable health conditions: The case of podoconiosis in Ethiopia.
Assess the feasibility of engaging youth to disseminate accurate information about gene by environmental (GxE) influences on podoconiosis, a neglected tropical lymphedema endemic in southern Ethiopia. A cross sectional survey was conducted with 377 youth randomly selected from 2 districts of Southern Ethiopia. Measures included GxE knowledge (4 true/false statements), preventive action knowledge (endorse wearing shoes and foot hygiene), causal misconceptions (11 items related to contagion) and confidence to explain GxE (9 disagree/agree statements). Over half (59%) accurately endorsed joint contributions of gene and environment to podoconiosis and preventive mechanisms (e.g., wearing protective shoes and keeping foot hygiene). Multivariable logistic regression showed that youth with accurate understanding about GxE contributors reported having: some education, friends or kin who were affected by the condition, and prior interactions with health extension workers. Surprisingly, higher accurate GxE knowledge was positively associated with endorsing contagion as a causal factor. Accuracy of GxE and preventive action knowledge were positively associated with youth's confidence to explain podoconiosis-related information. Youth have the potential to be competent disseminators of GxE information about podoconiosis. Interventions to foster confidence among youth in social or kin relationships with affected individuals may be most promising. Efforts to challenge youth's co-existing inaccurate beliefs about contagion could strengthen the link of GxE explanations to preventive actions.


Perioperative planning for two- and three-plane deformities.
Primary multiplanar external fixation is efficacious for a variety of fractures and may avoid a salvage situation. Complex deformity in conjunction with fractures, nonunions, and malunions can be measured and corrected with the Taylor Spatial Frame using the chronic and especially the total residual correction methods. Distal referencing-characterizing a deformed proximal fragment with respect to a normal distal fragment-is very useful in most lower-limb salvage cases. Corrections may be performed in stages using way points, and additional total residual corrections may be performed as needed. The same frame and analysis used for gradual correction may be used in conjunction with intramedullary nailing or plating in some cases.


Collagen synthesis by long-lived mRNA in embryonic chicken lens.
Lens capsule collagen synthesis by epithelial and fiber cells was examined by immunoprecipitation and collagenase digestion in embryonic and posthatch chicken eye lens. Epithelial cells and lens fibers in the process of terminal differentiation produce alpha 1 and alpha 2 type IV collagen chains. At 6 days of embryonic development in addition to the alpha 1 (IV) and alpha 2 (IV) collagen chains, lens cells produce high molecular weight collagenase-sensitive proteins not immunologically related to type IV collagen. Lens capsule collagen components have been identified in central and outer fibers isolated from 18-day embryos and from 10-day posthatch chicken eyes. At these stages, fibers which have an increasing number of picnotic nuclei still show collagen synthesis due to long-lived mRNA. Analysis of collagen synthesis by lens cells incubated with actinomycin D suggests that stabilization of collagen mRNA occurs in lens fiber cells and to a lesser extent in epithelial cells as early as 6 days of embryonic development.


DFT calculation and vibrational spectroscopic studies of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine.
The molecular structure of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine (BABP) was optimized by the DFT/B3LYP method with 6-311G (d,p), 6-311++G (d,p) and cc-pVTZ basis sets using the Gaussian 09 program. The most stable optimized structure of the molecule was predicted by the DFT/B3LYP method with cc-pVTZ basis set. The vibrational frequencies, Mulliken atomic charge distribution, frontier molecular orbitals and thermodynamical parameters were calculated. These calculations were done at the ground state energy level of BABP without applying any constraint on the potential energy surface. The vibrational spectra were experimentally recorded using Fourier Transform-Infrared (FT-IR) and micro-Raman spectrometer. The computed vibrational frequencies were scaled by scale factors to yield a good agreement with observed experimental vibrational frequencies. The complete theoretically calculated and experimentally observed vibrational frequencies were assigned on the basis of Potential Energy Distribution (PED) calculation using the VEDA 4.0 program. The vibrational modes assignments were performed by using the animation option of GaussView 05 graphical interface for Gaussian program. The Mulliken atomic charge distribution was calculated for BABP molecule. The molecular reactivity and stability of BABP were also studied by frontier molecular orbitals (FMOs) analysis.


Demonstration of subclinical left ventricular electrical and mechanical dysfunction in overweight subjects by frontal QRS-T angle and 3D-speckle tracking echocardiography.
Overweightness is a considerable step in the process leading to obesity. There are no sufficient studies on the effect of cardiomyopathy defined in obese patients about overweight subjects. We thought that it may be useful to examine the myocardial involvement in overweight individuals electro-mechanically with more sensitive techniques before the development of obesity cardiomyopathy. The aim of the present study was to demonstrate whether or not there are subclinical left ventricular (LV) electrical and mechanical dysfunctions in overweight patients using frontal QRS-T (fQRS-T) angle (electrically) and 3D-speckle tracking echocardiography (mechanically). A total of 80 overweight patients and 80 age- and sex-matched normal weight individuals were enrolled into the study. 3D-STE examinations of the patients were performed. Electrocardiographic recordings were obtained for fQRS-T angle assessment. The LV-GLS and LV-GCS were significantly depressed in the overweight group than in the normal weight group (-14.5 ± 3.4 vs. -21.7 ± 3.6, p < .001; -15.2 ± 4.6 vs. -24.3 ± 4.8, p < .001, respectively). The fQRS-T angle was found to be increased in the overweight group (142.5 ± 39.2 vs. 114.7 ± 43.5, p = < .001). Statistically significant positive linear correlations were observed between BMI with LV-GLS, LV-GCS, and fQRS-T angle. LV-GLS and LV-GCS were found to be disrupted linearly as BMI increased (r = .718 for BMI and LV-GLS, r = .653 for BMI and LV-GCS). As BMI increased, it was found that the fQRS-T angle increased (r = .692 for BMI and fQRS-T angle). Our results support that, overweight individuals, despite their being apparently healthy, may have subclinical LV myocardial mechanical and electrical dysfunction.


Anatomy and biomechanics of the medial patellofemoral ligament.
The medial patellofemoral ligament (MPFL) is a band of retinacular tissue connecting the femoral medial epicondyle to the medial edge of the patella. The MPFL is approximately 55 mm long, and its width has been reported to range from 3 to 30 mm. The MPFL is overlaid by the distal part of vastus medialis obliquus to a variable extent, and fibres of MPFL merge into the deep aspect of the muscle. Despite the MPFL being very thin, it had a mean tensile strength of 208 N, and has been reported to be the primary passive restraint to patellar lateral displacement. Lateral patellar displacement tests in vitro showed that the patella subluxed most easily at 20 degrees knee flexion. The contribution of the MPFL to resisting patellar lateral subluxation was greatest in the extended knee. This finding was linked to the retinaculae being tightest in full knee extension, and slackening with flexion.


Noninvasive Neuromonitoring Modalities in Children Part I: Pupillometry, Near-Infrared Spectroscopy, and Transcranial Doppler Ultrasonography.
Noninvasive neuromonitoring in critically ill children includes multiple modalities that all intend to improve our understanding of acute and ongoing brain injury. In this article, we review basic methods and devices, applications in clinical care and research, and explore potential future directions for three noninvasive neuromonitoring modalities in the pediatric intensive care unit: automated pupillometry, near-infrared spectroscopy, and transcranial Doppler ultrasonography. All three technologies are noninvasive, portable, and easily repeatable to allow for serial measurements and trending of data over time. However, a paucity of high-quality data supporting the clinical utility of any of these technologies in critically ill children is currently a major limitation to their widespread application in the pediatric intensive care unit. Future prospective multicenter work addressing major knowledge gaps is necessary to advance the field of pediatric noninvasive neuromonitoring.


Infants of very low birthweight. II: Perinatal factors in and conditions associated with respiratory distress syndrome.
The incidence and case fatality of certain neonatal conditions reported in 692 liveborn infants of birthweights 2000g or less born in South East London in 1970, 1971 and 1973 are presented. 210 (30.3 per cent) died in the neonatal period: respiratory disease and cerebral haemorrhage were the leading causes of death. 482 (69.7 per cent) survived. In these infants, jaundice, respiratory disease and biochemical disorders were the most frequently reported conditions. Because of the numerical importance of the respiratory distress syndrome, both as a single and as an associated diagnosis, a special study was made of predisposing factors. Gestational age, sex, condition of the infant assessed after birth, temperature of the infant on admission for care, and caesarean section were all shown to be independently associated with the incidence of respiratory distress. This confirms the views that the incidence could be reduced if particular attention were paid to the maintenance of body temperature, especially in those infants at risk by reason of the other factors identified.


Sagittal imbalance, muscle atrophy, and osteoporosis: risk factors for revision posterior lumbar fusion surgery in patients with Parkinson's disease.
The aim of our study was to evaluate features and complications of patients with Parkinson's disease (PD) who underwent posterior lumbar fusion surgery for lumbar degenerative diseases (LDD), as well as the risk factors for revision. Between January 2010 and December 2016, 132 patients were retrospectively identified for inclusion. Patients were divided into a 29 revision PD group and a 103 non-revision PD group. Patient factors included bone mineral density (BMD) and severity of PD using the Hoehn and Yahr staging system. Surgical factors included surgical levels and fusion methods. Radiographic measurements included pre-operative spinopelvic parameters, paraspinal muscle atrophy, and fatty infiltration. Logistic regression analysis was used to determine independent predictors for revision posterior lumbar fusion. The average age of the PD patients was 67.96 years, and the follow-up time was 49.01 months. R-PD patients accounted for 21.97% of all PD patients who underwent lumbar fusion surgery. Multivariable analysis indicated that low BMD (p = 0.012), fatty infiltration (p = 0.038), a smaller relative cross-sectional area (rCSA) of the paraspinal muscle (p = 0.008), larger pelvic incidence-lumbar lordosis (PI-LL) (p = 0.01), and sagittal vertical axis (SVA) (p = 0.004) were significant independent risk factors for revision posterior lumbar fusion in PD patients. PD patients with low pre-operative BMD, fatty infiltration, a smaller rCSA of the paraspinal muscle, and larger PI-LL and SVA had a higher rate of revision lumbar fusion. Maintaining sagittal balance, functional exercises, and anti-osteoporosis treatment were important in preventing complications in PD patients.


Computed tomographic fluoroscopy-guided transthoracic needle biopsy for diagnosis of pulmonary nodules.
The purpose of this study was to evaluate the usefulness of computed tomographic (CT) fluoroscopy-guided transthoracic needle biopsy (TTNB) with an 18-gauge automatic biopsy gun for the diagnosis of pulmonary nodules. Between March 1996 and January 1998, 50 patients in whom pulmonary lesions could not be diagnosed cytopathologically with fiberoptic bronchoscopy or were not clearly visualized with fluoroscopy underwent CT fluoroscopy-guided TTNB. Final pathological diagnoses were 23 lung carcinomas, five pulmonary metastases and 22 benign lesions. Sufficient tissue for analysis was obtained from 48 of the 50 lesions (96%). The overall diagnostic yield of CT fluoroscopy-guided TTNB was 90%. The sensitivity, specificity and accuracy for malignancy were 89%, 100% and 94%, respectively. In 20 of the 22 cases (91%) of benign lesions, histological analysis yielded correct and specific diagnoses. Complications occurred in 22 of the 50 cases (44%). The most common complication was pneumothorax, which occurred in 21 of the 50 cases (42%). Chest tube insertion was required in 6 (12%). Although CT fluoroscopy could not decrease the complication rate, CT fluoroscopy-guided TTNB with an automatic biopsy gun appears to be a promising technique for diagnosing pulmonary lesions, particularly benign lesions.


The effect of orexin a on the StAR, CYP11A1 and HSD3B1 gene expression, as well as progesterone and androstenedione secretion in the porcine uterus during early pregnancy and the oestrous cycle.
Orexin A (OXA) is primarily known for its involvement in the regulation of feeding behaviour, energy metabolism and sleep/wake cycle. Nevertheless, studies indicate its engagement in the regulation of the porcine reproductive system. Therefore, the aim of this study was to investigate OXA effect (1, 10, 100 nM), in the presence or absence of the selective orexin receptor type 1 antagonist (SB-3348667; 1 μM), on the gene expression of key steroidogenic enzymes: steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (CYP11A1) and 3β-hydroxysteroid dehydrogenase (HSD3B1), as well as on progesterone (P4) and androstenedione (A4) secretion. Endometrial and myometrial tissue explants were collected from gilts on days 10 to 11, 12 to 13, 15 to 16 and 27 to 28 of pregnancy, and on days 10 to 11 of the oestrous cycle (n = 5 per studied period of pregnancy or mid-luteal phase of the oestrous cycle). Gene expression was evaluated by real-time PCR. The level of steroid hormones secreted into the culture medium was examined by radioimmunoassay (RIA). In the present study, in the endometrium, OXA significantly stimulated StAR expression on days 12 to 13, CYP11A1 expression on days 27 to 28 and HSD3B1 expression on days 15 to 16 of pregnancy. Further, in this tissue, OXA decreased StAR mRNA level on days 10 to 11, CYP11A1 mRNA level on days 15 to 16, as well as HSD3B1 mRNA level on days 10 to 11 and 12 to 13 of gestation. Regarding the myometrium, OXA stimulated CYP11A1 gene expression on days 15 to 16 of pregnancy. In this tissue, OXA decreased StAR transcript content on days 15 to 16 and CYP11A1 mRNA level on days 27 to 28. We also demonstrated that OXA alone enhanced P4 secretion in the endometrium on days 10 to 11 and 12 to 13 of gestation. OXA alone has no significant effect on endometrial and myometrial A4 secretion, whereas OXA in combination with OX1R antagonist increased this hormone secretion during all studied stages of pregnancy. Therefore, we can conclude that OXA may affect de novo synthesis and secretion of P4 and A4 in the porcine uterus via participating in the regulation of key steroidogenic enzymes gene expression, as well as modulating steroid hormones secretion during early pregnancy and mid-luteal phase of the oestrous cycle in pigs. However, further research is required to explain the exact role of OXA in the porcine uterus.


Can zinc pollution promote adaptive evolution in plants? Insights from a one-generation selection experiment.
Human activities generate environmental stresses that can lead plant populations to become extinct. Population survival would require the evolution of adaptive responses that increase tolerance to these stresses. Thus, in pseudometallophyte species that have colonized anthropogenic metalliferous habitats, the evolution of increased metal tolerance is expected in metallicolous populations. However, the mechanisms by which metal tolerance evolves remain unclear. In this study, parent populations were created from non-metallicolous families of Noccaea caerulescens. They were cultivated for one generation in mesocosms and under various levels of zinc (Zn) contamination to assess whether Zn in soil represents a selective pressure. Individual plant fitness estimates were used to create descendant populations, which were cultivated in controlled conditions with moderate Zn contamination to test for adaptive evolution in functional traits. The number of families showing high fitness estimates in mesocosms was progressively reduced with increasing Zn levels in soil, suggesting increasing selection for metal tolerance. In the next generation, adaptive evolution was suggested for some physiological and ecological traits in descendants of the most exposed populations, together with a significant decrease of Zn hyperaccumulation. Our results confirm experimentally that Zn alone can be a significant evolutionary pressure promoting adaptive divergence among populations.


Pediatric urolithiasis in Morocco: Composition of 432 urinary calculi analyzed by infrared spectroscopy.
Incidence of pediatric urolithiasis is decreasing in most developing countries where endemic bladder stones are less prevalent than in the past years. In parallel, stone composition has changed. Only few data are available in North Africa, except for Tunisia. We report stone composition in the Moroccan pediatric population. Composition of 432 stones from children (302 boys, 130 girls) was determined by infrared spectroscopy. The samples were collected during the period 1999-2016. Stone morphology, which is an important aspect for etiology was determined by examination of each stone under a stereomicroscope. Stone composition was compared to patients' age and gender. The global male-to-female ratio was 2.32. Regarding stone composition, calcium oxalate was the main component in 51.6% of the stones, followed by struvite (18.1%), ammonium urate (9.5%) and carbapatite (9%). Significant differences were found between males and females: calcium oxalate accounted for 72.3% of stones in girls and 42.7% in boys (P<10-6); conversely, struvite was more frequent in boys than in girls (22.2 vs 8.5%, P<10-4). The same was found for calcium phosphate stones (11.9% in boys; 4.6% in girls, P<0.05). Stone morphology helped us for detecting several pathological conditions: type Ic whewellite stones, as a marker for primary hyperoxaluria, was found in 17.6% of stones and type IIId ammonium urate stones, suggestive for infectious diarrhea, was identified in 20.1% of all stones. This is the largest series of pediatric stones in Morocco studied by infrared analysis and morphological examination. 3.