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Background: An intrauterine contraceptive device is suitable for women of all reproductive age groups for preventing unwanted pregnancies. Immediate post partum family planning services need to be emphasized where in the woman leaves the hospital with safe and effective contraception in place. Despite the accepted demand for post partum family planning, many women do not access the services they need prevent unintended pregnancies. Objective: To assess utilization of immediate postpartum intrauterine contraceptive device and associated factors among women who gave birth at government hospitals of Gamo Zone, Southern Ethiopia. Method: Facility-based crosses sectional study was conducted from March 1 to 30 of 452 participants were studied using systematic random sampling technique. Data were entered into Epi-data v. 4.2.2.1 and exported to SPSS v.23 for analysis. Crude or adjusted odds ratio, and 95% confidence interval were used to assess the strength of association and statistical significance. Variables which had a p-value of ≤0.25 in bivariate analysis were considered as candidates for multivariate regression analysis; variables that had a p-value of ≤0.05 in the multivariate analysis were considered as independent factors associated with utilization of immediate postpartum intrauterine contraceptive device among parturients in the final multiple logistic regression analysis. Results: This finding revealed that about 161 (36%) of the respondents had showed willingness to use immediate PPIUD, however, only about 62 (14%) of study participants were utilized immediate PPIUCD. Mothers who did not plan to have another child (AOR = 2.84, 95% CI, (1.12, 7.21), undecided plan to have another child (AOR = 2.55, 95% CI, (1.21, 5.35), counselled about PPIUCD (AOR=4.35, 95% CI, (2.11, 8.96) and completed ANC follow up (AOR=2.43, 95% CI, (1.28, 4.60) were associated with immediate post partum contraceptive device utilization. Conclusion and Recommendation: Even though 58% and 53% of the mothers were counselled and completed antenatal service respectively but efforts need to improve antenatal care service and integrate counselling service through the whole cascade of pregnancy.

Primary cilia are single non-motile organelles that provide a highly regulated compartment into which specific proteins are trafficked as a critical part of various signaling pathways. The absence of primary cilia has been shown to prevent differentiation of human mesenchymal stem cells (hMSCs). Changes in primary cilia length are crucial for regulating signaling events; however it is not known how alterations in cilia structure relate to differentiation. This study tested the hypothesis that changes in primary cilia structure are required for stem cell differentiation. hMSCs expressed primary cilia that were labeled with acetylated alpha tubulin and visualized by confocal microscopy. Chemically induced differentiation resulted in lineage specific changes in cilia length and prevalence which were independent of cell cycle. In particular, adipogenic differentiation resulted in cilia elongation associated with the presence of dexamethasone, while insulin had an inhibitory effect on cilia length. Over a 7-day time course, adipogenic differentiation media resulted in cilia elongation within 2 days followed by increased nuclear PPARγ levels; an early marker of adipogenesis. Cilia elongation was associated with increased trafficking of insulin-like growth factor-1 receptor β (IGF-1Rβ) into the cilium. This was reversed on inhibition of elongation by IFT-88 siRNA transfection, which also decreased nuclear PPARγ. This is the first study to show that adipogenic differentiation requires primary cilia elongation associated with the recruitment of IGF-1Rβ onto the cilium. This study may lead to the development of cilia-targeted therapies for controlling adipogenic differentiation and associated conditions such as obesity. Stem Cells 2015;33:1952–1961

Graphical abstract, The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery applications. Statement of Significance The surface topography of synthetic biomaterials plays important roles in material-driven osteogenesis. The data presented herein have shown that the surface topography of calcium phosphate ceramics regulates mesenchymal stromal cells (e.g., human bone marrow mesenchymal stromal cells, hBMSCs) with respect to morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation in vitro. Together with bone formation in vivo, our results suggested a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery by the bioengineering control of osteogenesis via primary cilia modulation.

This paper presents the main features of the pilot solar power plant under construction in Sardinia (Italy), which is based on concentrating solar power and concentrating photovoltaic plants with energy storage. The plant was developed with the aim of produce electricity with desired power profiles in accordance with weather forecasting.

Yogun bir rekabetin yasandigi is dunyasinda firmalar surekliliklerini saglamak icin tedarik zinciri yonetimi kavramina oldukca fazla onem vermeye baslamislardir. Bu surecte, zincir uyelerinin tek bir isletme gibi hareket edebilmesi neticesinde maliyetler azalmakta, belirsizlikler ortadan kalkmakta ve isletmelerin rekabet gucleri artmaktadir. Son donemlerde moda ve hazir giyim sanayinin yapisi, mevcut sezonlara ara sezonlar ekleyerek, musteriye daha cesitli secenekler sunmayi hedefleyen hizli moda kavramina dogru yonelmektedir. Bu yolla musteriye daha dusuk fiyatlar sunulmakta, satis miktarlari, kar ve marka bilinirligi artmaktadir. Bu calismada, hizli moda sektorunde uygulanmak uzere, tedarik zincirinin ceviklik ve esneklik boyutlariyla firma performansi arasindaki iliskiyi ortaya koyan bir model gelistirilmis ve modelde yer alan hipotezler coklu regresyon analizi ile test edilmistir.

Bortezomib (BTZ), a selective proteasome inhibitor, is an antitumor drug used to treat multiple myeloma. As a side effect, BTZ determines a painful peripheral neuropathy (PPN), often refractory to management. Chronic BTZ administration in female Wistar rats induced a PPN in which the development of mechanical allodynia is associated to an increase in the expression of TRPV1 and CGRP in the dorsal root ganglia (DRG) and spinal cord dorsal horn. In this study we examine the possible role of two standard analgesics, Gabapentin (Gaba) and buprenorfin (Bupre), in modulating the expression of TRPV1 and CGRP in the DRG and spinal cord of rats chronically treated with BTZ. To this aim, female Wistar rats were treated with BTZ 0.20 mg/kg, 3 times a week for 8 weeks (i.v.). Then Gaba (100 mg/kg, daily, p.o.) and Bupre (28,8 µg/kg, daily, s.c.) were orally administered in a curative schedule for 2 weeks. The expression of TRPV1 and CGRP, a neuropeptide involved in nociceptive neurotransmission, was examined in L4-L5 DRG and spinal cord segments by means of western blot (WB) and immunohistochemistry. WB analysis did not show any statistically significant change of protein levels in DRG and spinal cord. Instead, chronic BTZ treatment followed by a 2 weeks follow-up period affected TRPV1 expression by inducing an increase in the proportion of TRPV1-like immunoreactive (LI) DRG neurons, whereas did not affect the percentage of CGRP-LI neurons. Labeled perikarya were mostly of small- and medium-size. No BTZ-induced changes in immunolabeling were appreciable in the dorsal horn of the spinal cord. Treatment with Gaba and Bupre reduced levels of TRPV1 protein in spinal cord homogenates, whereas had no effect on DRG protein levels. None of the analgesics appeared to reverse in a statistically significant way the BTZ-induced increase of labelled DRG neurons nor induced any change in the detectability of positive innervation in the spinal cord dorsal horn.

Bortezomib (BTZ), a selective proteasome inhibitor, is a potent antineoplastic drug to treat multiple myeloma. In clinical practice, the most significant side effect of its administration, is a peripheral painful sensory neuropathy (PN), characterized by numbness and tingling in a distal stocking-glove distribution as well as distal paresthesia and generally associated with impairment of Adelta and C type primary afferent fibers. At the moment the therapies for PN are not really effective and almost only symptomatic. To evaluate if BTZ-induced sensory deficits are associated to loss of epidermal nerve fibers as is observed in other PN conditions, here we examine the effect of a well-established chronic BTZ-treatment schedule on the number of intraepidermal nerve fibers (IENF) in a rat model of BTZ-induced PN and compared the outcome of chronic BTZ-treatment followed by two-weeks of follow up with that of animals that received a 2-weeks treatment period with two analgesic drugs commonly used in clinical practice such as Gabapentin (Gaba) and buprenorphine (Bupre). To these aims, female Wistar rats were treated with BTZ 0.20 mg/kg, 3 times a week for 8 weeks (i.v.). Then analgesic were orally administered according to the following curative schedule: Gaba (100 mg/kg, daily, p.o.), Bupre (28,8 μg/kg, daily, s.c.). At the end of treatments, the hindlimb footpad skin was examined by immunohistochemistry for the pan-neuronal marker PGP9.5 and the neuropeptide calcitonin gene-related peptide (CGRP), a neuropeptide involved in pain perception and neurotransmission. Labelled nerve fibers were distributed in the reticular and papillary dermis and within the epidermal lining. Quantitative evaluation of IENF showed that, according to the painful symptoms induced by BTZ, the mean linear density of CGRP-labelled IENF normalized by that of the PGP9.5-labelled ones shows a statistically significant decrease in BTZ-treated rats. None of the analgesics used in this study appeared to reverse the BTZ-induced loss of IENF. Results obtained suggest that the CGRP-positive innervation is likely involved in the persistence of BTZ-induced pain and that detectability of CGRP-positive IENF appears not to be related to the effectiveness of the selected analgesics.

Bortezomib (BTZ) is a proteasome inhibitor used as first-line therapy for multiple myeloma. However, its administration induces the development of severe painful peripheral neuropathy (PPN). This painful condition is an important medical need since the available treatments are actually ineffective. We recently described a mice model of PPN that shares most of the conditions found in patients treated chronically with BTZ (Carozzi et al., 2013). In fact, BTZ determines dysfunction of all fiber types in sensory nerves and, at least in mice, alters the electrical activity of the spinal dorsal horn neurons. This alteration of the basal electrophysiological activity induces also relevant changes in the central nociceptive transmission. In this work we characterize the neuroprotective effects of an imidazoline receptor 2 ligand (CR4056) able to allosterically inhibit the activity of monoamine oxidase-A, a key enzyme in the regulation of neuropathic pain. Wistar rats were treated with BTZ 0.20 mg/kg, 3 times a week for 8 weeks (i.v). Then CR4056 was orally administered in a curative schedule at 6 mg/kg, once a day, for 2 weeks. Gabapentin (100 mg/kg, daily, p.o.) and buprenorphine (28,8µg/kg, daily, s.c.) were used as internal analgesic standards. At the end of both BTZ and analgesic treatments, we measured the caudal and sciatic nerve conduction velocity (NCV), the morphological/morphometrical alterations in the caudal nerve and the neuropathic pain development. BTZ treatment induced a significant impairment of sensory, but not motor NCV, slight hyperalgesia, significant mechanical allodynia and clearing of myelinated fibers in the caudal nerves. After two weeks of follow up animals did not spontaneously recover functional, morphological and behavioral abnormalities while the 2 weeks-treatment with CR4056 (but not with gabapentine and buprenorphine) significantly resolved BTZ-induced mechanical allodynia. Results obtained show that CR4056 produces a marked analgesic effects against BTZ-induced neuropathic pain without signs of tolerance. Carozzi VA, Renn CL, Bardini M. et al. PLoS One. 2013; 8(9):e72995.

To extend our previous observations on the beneficial effect of dietary Pistacia lentiscus L. essential oil during cerebral bilateral common carotid artery occlusioninduced injury, we evaluated the activity of one of its major components, beta-caryophyllene (BCP), already known to possess peculiar biological activities, in Wistar rat cerebral cortex. Cerebral hypoperfusion was produced by a 30 min bilateral common carotid artery occlusion followed by 60 min reperfusion (BCCAO/R). Animals were starved for 12 hours before surgery and, 6 hours prior to hypoperfusion, BCP (40 mg/kg/0, 45 ml of sunflower oil as vehicle) was administered via gavage. Biological samples of brain tissue, plasma and cerebrospinal fluid (CSF) were examined by HPLC, western blot, gel zymography and immunohistochemistry and analyzed for fatty acids, expression of the enzyme ciclooxygenase-2 (COX-2), CB receptors for endocannabinoids (eCBs), and peroxisome proliferator-activated receptor (PPAR)-alpha and enzymatic activity of matrix-metalloprotease-9 (MMP9). Data obtained indicate that BCP appears to influence the outcome of BCCAO/R cerebral injury by modulating changes in levels of polyunsaturated fatty acids, biosynthesis of eCBs and eCB congeners, expression of CB1 and CB2 receptors, COX-2 protein levels and enzymatic activity of MMP9. Brain tissue response to the hypoperfusion/reperfusion-induced cerebral insult is modulated by dietary administration of BCP, suggesting the possible use of this molecule as nutritional treatment in neuroprevention. Work funded by Fondazione Banco di Sardegna., Italian Journal of Anatomy and Embryology, Vol 119, No 1 (Supplement) 2014

This study is aimed to further characterize on a neurochemical, histological and morphometric ground the human Locus K, a newly identified region in the human nucleus cuneatus that shares neurochemical features with protopathic second order sensory nuclei (Del Fiacco et al., 2013; Serra et al., 2013). Human brainstem sections were observed by means of ABC immunohistochemistry for calcitonin gene-related peptide (CGRP), substance P (SP) and transient receptor potential vanilloid type-1 receptor (TRPV1), Kluver-Barrera, Black Gold kit II and Nissl staining followed by computerized analysis of cell size and density. As for CGRP and SP, at both pre- and postnatal age, immunoreactivity to TRPV1 occurs in Locus K with a distribution alike that present in the spinal trigeminal nucleus, caudal part. Morphometric analysis shows that, in adult tissue, the mean diameter and density of Nissl stained neurons in the Locus K are consistent with those of the caudal spinal trigeminal and solitary nuclei, and different from those in the gracile, cuneate and external cuneate nuclei. Kluver-Barrera and Black Gold kit II staining shows that myelinated fibres, abundant in the main cuneate, gracile and trigeminal magnocellular nuclei, are scarce in both the Locus K and trigeminal substantia gelatinosa. Immunohistochemical and cyto- and myeloarchitectural analysis uphold the parallel neurochemical and structural arrangement for Locus K and protopathic nuclei in the human medulla oblongata, and support the concept that Locus K represents a special component of the human dorsal column nuclei. Work funded by Fondazione Banco di Sardegna., Italian Journal of Anatomy and Embryology, Vol 119, No 1 (Supplement) 2014

Locus K is a newly identified region within the territory of the human nucleus cuneatus that shares neurochemical and histological features with protopathic second order sensory nuclei (Del Fiacco et al., 2013; Serra et al., 2013; SIAI 2014). This work is aimed at examining the rat dorsal column nuclei in order to ascertain whether a structure homologous to the human Locus K occurs in the rat brain. Rat brainstem sections were observed by means of ABC and fluorescence immunohistochemistry for neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), Kluver-Barrera and Nissl staining. Results of the peptide immunoreactive structures in the rat dorsal column nuclei are in general good agreement with findings in previous studies (Hoeflinger et al., 1993). However, at caudalmost levels of the complex, in the territory of the cuneate fascicle and dorsal to the caudal pole of the cuneate nucleus, a small column of gray matter area can be identified that contains a dense plexus of varicose labelled nerve fibres. The observed discrete region has never distinctly described beforehand. Both its position and aspect at neuropeptide-immunoreactivity resemble those of the Locus K we detected in the human dorsal column nuclei, allowing the possibility that it represents the its homologous nucleus in the rat brain. Work funded by Fondazione Banco di Sardegna., Italian Journal of Anatomy and Embryology, Vol 119, No 1 (Supplement) 2014

In this study Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, was tested for its protective effects in cerebral ischemia/reperfusion-induced injury in Wistar rat frontal cortex and plasma. Cerebral ischemia was produced by a 20 min bilateral common carotid artery occlusion followed by 30 min reperfusion. Pistacia lentiscus L. essential oil (E.O.) (200 mg/0, 45 ml of sunflower oil as vehicle) was administered via gavage 6 hours prior to ischemia. Rats were randomly assigned to four groups, ischemic/reperfused (I/R) and sham-operated rats treated with the vehicle or with E.O.. Different brain areas were analysed for fatty acid changes and expression of the enzyme cyclooxygenase-2 (COX-2). Ischemia/reperfusion triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid (HPUFA) most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of COX-2, as assessed by Western Blot. In plasma of ischemic/reperfused rats, E.O. administration increased both the DHA-to-eicosapentaenoic acid (EPA) ratio and levels of the endocannabinoid congeners palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). The results obtained suggest that ischemia/reperfusion triggers a cerebral insult sufficient to cause a a region specific lipid peroxidation as evidenced by the detectable, significant decrease in the tissue level of DHA, the most abundant essential fatty acid of neuronal membrane phospholipids. Acute dietary pre-treatment with E.O. triggers modifications both in the frontal cortex, where COX-2 expression decreases and the decrease of DHA is apparently prevented, and in plasma, where PEA and OEA levels increase. We suggest that the activity of PEA and OEA, as endogenous ligands of the peroxisome proliferator-activated receptor (PPAR)-alpha, by inducing the peroxisomal beta oxidation, may explain the observed increase in the DHA/EPA ratio. The latter, in fact, might account for an increased metabolism of n-3 aimed at restoring DHA within damaged brain tissue. The possibility that changes in fatty acid metabolism and plasmatic availability of PEA and OEA are correlated events represents an issue worth future investigations., Italian Journal of Anatomy and Embryology, Vol 116, No 1 (Supplement) 2011

The integration of small scale concentrating solar power (CSP) in an industrial district, in order to develop a microgrid fully supplied by renewable energy sources, is presented in this paper. The plant aims to assess in real operating conditions, the performance, the effectiveness and the reliability of small-scale concentrating solar power technologies in the field of distributed generation. In particular, the potentiality of small scale CSP with thermal storage to supply dispatchable electricity to an industrial microgrid will be investigated. The microgrid will be realized in the municipal waste treatment plant of the Industrial Consortium of Villacidro, in southern Sardinia (Italy), which already includes a biogas power plant. In order to achieve the microgrid instantaneous energy balance, the analysis of the time evolution of the waste treatment plant demand and of the generation in the existing power systems has been carried out. This has allowed the design of a suitable CSP plant with thermal storage and an electrochemical storage system for supporting the proposed microgrid. At the aim of obtaining the expected energy autonomy, a specific Energy Management Strategy, which takes into account the different dynamic performances and characteristics of the demand and the generation, has been designed. In this paper, the configuration of the proposed small scale concentrating solar power (CSP) and of its thermal energy storage, based on thermocline principle, is initially described. Finally, a simulation study of the entire power system, imposing scheduled profiles based on weather forecasts, is presented.

The fast increasing share of distributed generation from non-programmable renewable energy sources, such as the strong penetration of photovoltaic technology in the distribution networks, has generated several problems for the management and security of the whole power grid. In order to meet the challenge of a significant share of solar energy in the electricity mix, several actions aimed at increasing the grid flexibility and its hosting capacity, as well as at improving the generation programmability, need to be investigated. This paper focuses on the ongoing preliminary studies at the Ottana Solar Facility, a new experimental power plant located in Sardinia (Italy) currently under construction, which will offer the possibility to progress in the study of solar plants integration in the power grid. The facility integrates a concentrating solar power (CSP) plant, including a thermal energy storage system and an organic Rankine cycle (ORC) unit, with a concentrating photovoltaic (CPV) plant and an electrical energy storage system. The facility has the main goal to assess in real operating conditions the small scale concentrating solar power technology and to study the integration of the two technologies and the storage systems to produce programmable and controllable power profiles. A model for the CSP plant yield was developed to assess different operational strategies that significantly influence the plant yearly yield and its global economic effectiveness. In particular, precise assumptions for the ORC module start-up operation behavior, based on discussions with the manufacturers and technical datasheets, will be described. Finally, the results of the analysis of the: “solar driven”, “weather forecasts” and “combined storage state of charge (SOC)/ weather forecasts” operational strategies will be presented.

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established “chronic” schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.

This paper presents the results of management-oriented research on energy, forest, and human health issues in a remote mountain area, the Sagarmatha National Park and Buffer Zone (SNPBZ), Nepal. The research was based on a broader, integrated participatory framework ultimately intended for use in adaptive management. The present study focused on the application of a participatory modeling framework to address problems related to energy demand and consumption, forest condition, and indoor air pollution, which were defined by the stakeholders as important issues to be addressed. The models were developed using a generalizing design that allows for user-friendly adaptation to other contexts (free download at http://hkkhpartnership.org). Moreover, we simulated management scenarios in collaboration with all modeling actors with the aim of building consensus on the understanding of the system as well as supporting decision-makers' capacity not only to respond to changes, but also to anticipate them. Importantly, the system dynamics assessment found that the SNPBZ forests are affected by an increasing demand for fuelwood (occurring due to tourism growth), as one of the main sources of energy. Selected forests show an average reduction of 38% in forest biomass from 1992 to 2008. This shows that the business-as-usual scenario is unlikely to result in the preservation of the current forest status; in fact, such preservation would require 75% of fuelwood to be replaced with alternative energy sources. At the same time, a 75% reduction of fuelwood use (and an 80% reduction of dung use) would reduce indoor carbon monoxide (CO) concentrations to the standard limits for CO exposure set by the World Health Organization.