There are four principal arboviruses in mainland China. Two kinds of them are mosquito-borne viruses, namely Japanese encephalitis virus and dengue virus, which lead to Japanese encephalitis, and dengue fever/dengue hemorrhagic fever respectively; the other two are tick-borne viruses, namely tick-borne encephalitis virus and Crimean-Congo hemorrhagic fever virus , which contribute to tick-borne encephalitis and Xinjiang hemorrhagic fever respectively. With exception of these four main arboviruses, many other mosquito-associated viruses have been isolated and identified in recent years. These newly isolated and identified mosquito-associated viruses are probably responsible for human and animal infections and diseases. The purpose of this review is to describe the newly isolated mosquito-associated viruses in mainland China which belong to five viral families, including their virological properties, phylogenetic relationships, serological evidence, as well as to appeal the public health concentration worldwide. Arboviruses comprise a group of viruses that reproduce in sensitive blood-sucking arthropods . There aSince the 1950 s, four kinds of arbovirus-related diseases have been confirmed to be endemic in China, namely Japanese encephalitis (JE), dengue fever (DEN), tick-borne encephalitis (TBE) and Crimean-Congo hemorrhagic fever (CCHF)  -10. The This article focuses on the mosquito-associated viruses isolated from variety of arthropods, humans and animals that have been identified in mainland China in recent years, which belong to 5 viral families, and a lot of them are important zoonotic pathogens Figure .Culex spp. mosquitoes collected from corrals in Xinjiang, China, in the summer of 2006 by Lu et al. YUOV is a newly identified member of genus oviridae . It was articles . The vir species . In receBrevidensoviruses within the family Parvoviridae was firstly isolated from Culex pipiens pallens in Liaoning province. Additional strains of CppDNV were subsequently isolated from various provinces of China , Culex pipiens quinquefasciatus (two strains), Culex tritaeniorhynchus (three strains), Anopheles sinensis (one strain), unclassified Culex mosquitoes (six strains) and other miscellaneous mosquitoes (two strains) from the Liaoning, Yunnan, Xinjiang and Guizhou provinces in China demonstrated a nucleotide homology of more than 98%. This confirmed that the virus was a newly identified member of the species Aedes aegypti densovirus (AaeDNV) along with the previously identified Aedes albopictus densovirus  [During an investigation of arboviruses in China, a new kind of virus with the same biological characteristics and a genome sequence very similar to the viruses belonging to the genus na Table . The viralDNV-2) .Culex pipiens pallens, Culex modestus, Culex tritaeniorhynchus, Aedes (Och.) detritus, Aedes vexans, Aedes dorsalis, Aedes albopictus, Anopheles philippinensis, Anopheles sinensis and Armigeres obturbans. Of this growing list of arboviruses, most are mosquito borne. The ability of such viruses to spread between geographic regions through movements of people, animals and goods means that addressing them clinically is of great public health importance. Given the increasingly frequent international exchanges with China, the risk for further introduction and exportation of the mosquito-borne viruses via human activity and transportation of goods becomes greater, so enhanced monitoring and long-term surveillance of these viruses are of great public health importance both in China and internationally.In the last two decades, 12 species of viruses belonging to five families have been newly identified in mainland China. Four  are pathogenic to humans and livestock. Four  are initially isolated and identified in China and are considered to be potential threats to humans and livestock. One (CHIKV) is an imported virus, and no autochthonous cases have been reported in mainland China to date. One (GETV) is known as a pathogen in horses and pigs. Two (KDV and CppDNV) are associated with insects and are not pathogenic to humans. These species of viruses have been isolated from ten mosquito species in four genera, including The authors declare that they have no competing interests.HL and XYG contributed equally to the analysis and interpretation of the results, and involved in drafting the manuscript. Both of them have read and approved the final version of the manuscript. Dr. GDL contributed to conception and design of the manuscript, and involved in drafting and revising the manuscript as well as gave final approval of the version to be published.


The role of scientific evidence in influencing political decisions that affect the future and the importance of research in generating such evidence is highlighted in the context of the Swiss federation. Within the Swiss federation the responsibilities are balanced between the confederation and the cantons. Currently Switzerland faces several challenges such as epidemiological transition, increase in chronic non-communicable diseases, increasing social costs, increasing health care costs, need for more medical professionals and health inequalities. Therefore we need more scientific knowledge to tackle these problems. Considerable investment in research infrastructure is needed in the form of cohorts and biobanks. Two new federal laws have been enacted which pertain to prevention, health promotion, managed care and disease management. However such laws need scientific support and collaboration across political, economic, academic and social forces.


A 20-week fetus was diagnosed with tetralogy of Fallot and multicystic kidneys. The postmortem study showed missing müllerian structures with small streak ovaries, external male genitalia, and an abnormal cloacal septation (imperforate anus with a sigmoid colon opening in the bladder). As the observed anomalies were related with septation, a mechanism related with the activation of specific growth factors, we discuss the possibility of a disorder in the function of the bone morphogenetic proteins as a common cause for the widespread anomalies found in this fetus.  In the embryo heart, the conotruncal and atrioventricular cavities are divided by mean of endocardial cushions, forming the 4 chambers and the outflow tracts. Similarly, in the cloaca, a septation occurs when the mesoderm of the urorectal septum grows in an apical basal direction forming the bladder and the rectum. In the kidney, however, the opposite mechanism applies, as no septation is expected when the ureteric bud branches within the metanephric mesenchyme . SeptatiA 23-year-old woman in her first pregnancy with an ordinary follow-up and no previous medical history attended our ultrasound unit for a 20-week scan. The sonographic findings  Figures  and 2 diWe were not able to find a common etiology for the association of malformations seen in this fetus; however, the observed anomalies seemed to be related with septation, a mechanism recently related with the progressive activation of specific growth factors. Although several molecules have been involved in this process, the bone morphogenetic proteins (BMPs), growth factors belonging to the ß-TGF superfamily, have become increasingly important. Concerning our case, they drew our attention as (1) in the heart, BMPs- and BMP-type II receptors are needed for septation of the outflow tract, and BMPs malfunction causes conotruncal anomalies , (2) in BMPs and many other growth factors initiate, conduct, and finalize septation processes in the human body. It seems therefore plausible that any disturbance of the molecules in charge of these systemic processes may cause widespread anomalies of septation . Also, we were unable to find a known etiology for the existence of a female pseudohermaphroditism as there was no history of hormonal intake, and the genetic tests for the SRY translocation and 21 hydroxylase deficiency were negative. However, anomalies of the cloaca in association with female pseudohermaphroditism have been previously reported –8, somet


Research on the functions of the amygdala has pointed towards multifaceted roles in learning, emotion, attention and decision making. The degree to which the various functions of the amygdala reflect different aspects of a common set of operations, such as the modulation of attention, remains unknown. A recent observation links deficits in facial expressions following bilateral amygdala damage to a specific attentional mechanism, reflected in an abnormal pattern of gaze directed to faces , raising


Training increased willingness of healthcare workers to care for patients with all types of communicable diseases. Construction of new BioSafety Level (BSL) 3 and 4 laboratories has raised concerns regarding provision of care to exposed workers because of healthcare worker (HCW) unfamiliarity with precautions required. When the National Institutes of Health began construction of a new BSL-4 laboratory in Hamilton, Montana, USA, in 2005, they contracted with St. Patrick Hospital in Missoula, Montana, for care of those exposed. A care and isolation unit is described. We developed a training program for HCWs that emphasized the optimal use of barrier precautions and used pathogen-specific modules and simulations with mannequins and fluorescent liquids that represented infectious body fluids. The facility and training led to increased willingness among HCWs to care for patients with all types of communicable diseases. This model may be useful for other hospitals, whether they support a BSL-4 facility, are in the proximity of a BSL-3 facility, or are interested in upgrading their facilities to prepare for exotic and novel infectious diseases. Over the past decade, biomedical research performed on agents of viral hemorrhagic fevers (VHFs) has substantially increased. These agents are members of several virus groups, including filoviruses , Old World arenaviruses , New World arenaviruses , flaviviruses , and bunyaviruses  . On several occasions, persons naturally infected with a VHF agent have sought treatment at hospitals located in industrialized areas of the world  at the US Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, USA, or the biocontainment patient care unit at Emory University, Atlanta, Georgia, USA. The benefits of a remote facility include reducing the risk for nosocomial transmission, use of personnel who are already trained in managing a patient in containment, and control of public access  recently completed construction of an integrated research facility with BSL-4 research space at its Rocky Mountain Laboratories (RML) in Hamilton, Montana. As part of the project, NIAID contracted with St. Patrick Hospital and Health Sciences Center (SPH), a regional referral medical center located in Missoula, Montana, for provision and staffing of a patient isolation facility to support the RML BSL-4 research program. The facility, known as a care and isolation unit (CIU) (>12 air exchanges per hour to the patient rooms (including >2 outside air changes per hour); 5) passage of exhaust through a HEPA filter to the building exterior >8 feet above the rooftop and well removed from air intake ducts; 6) room surfaces constructed of seamless materials amenable to topical disinfection; 7) the capability for the full range of intensive care unit (ICU) monitoring and support, including the ability to perform limited surgery, hemodialysis or peritoneal dialysis, Swan-Ganz catheter placement, and hemodynamic monitoring; and 8) a separate autoclave within the CIU for sterilizing all items that come out of a patient room.To satisfy the NIH requirements for the CIU, the following elements were needed: 1) access control, i.e., the ability to restrict entrance into the CIU to authorized persons only; 2) three separate stand-alone rooms, each with a bathroom and shower, separate air handling, and an anteroom separating the patient room from the hallway; 3) directional air flow from the hallway into the anteroom and from the anteroom into the patient room; 4) a dedicated exhaust system providing SPH was selected to provide these services and facilities. SPH is a not-for-profit medical center under the sponsorship of the Sisters of Providence. It has 195 acute care beds, and >10,000 patient admissions per year. The full range of standard specialty medical care is available within the hospital, including 24 hour, 7 day/week availability of specialists in critical care, infectious disease, and all surgical subspecialties.SPH retrofitted 3 adjacent rooms within the existing medical ICU (MICU) to create the CIU. A set of doors was installed to control access to the CIU from the MICU, and these would remain open when the CIU was not in use . A separIn addition to the physical aspects of the CIU, several other elements were developed. Specific policies and procedures were written that deal with all aspects from admission to discharge, including unique aspects such as clean up of infected bodily spills, donning and doffing of personal protective equipment (PPE), and use of the autoclave. Support of hospital administration, physicians, nurses, and support personnel was critical. This backing was enlisted primarily by mounting an educational campaign that stressed the true risk for nosocomial transmission of these agents, as well as the recognition that the increased resources that would be provided to the hospital could greatly enhance capacity for handling community-acquired infections.One feature dealt with preparing the hospital staff to care for such exposed persons. To accomplish this feature, we developed a detailed curriculum, which can be presented during a 1-day training workshop. This workshop includes didactic information, patient care scenarios discussed in group settings, and hands-on training. Simulation of various patient care activities  is conducted by using programmable mannequins and either tonic water or Glo Germ , both of which fluoresce under ultraviolet light, to simulate infectious body fluids. Continuing education credits are granted for participation. Competence is maintained with quarterly demonstration of proper technique, review of CIU-specific policies and procedures, and required utilization of a series of online problem-oriented patient care scenarios. Training videos have been developed that demonstrate proper technique for spill cleanup, donning and doffing of PPE, processing of patient specimens, and processing of biohazardous waste, including use of the autoclave. Finally, detailed educational modules have been developed for each of the BSL-4 pathogens. These modules are designed to provide a nurse, emergency medical technician, or critical care physician with critical information that is quickly accessible as well as an extensive discussion of all aspects of the agent. The modules are in a standard format with extensive references and websites for further reading. All of this information is available for review any time both in hard copy as well as on the hospital’s intranet site in the form of slide presentations, videos, or PDF files. The SPH staff has been generous in supplying feedback on the training and has been instrumental in refining the curriculum. Acquisition of knowledge has been documented with the use of pretesting and posttesting. After completion of the training, SPH staff members expressed increased confidence in caring for patients with all types of communicable infectious diseases, including VHFs.To maintain readiness, a series of drills and exercises have been performed and will continue, in collaboration with RML and local emergency medical services providers. These readiness exercises have encompassed all aspects of care from arrival to the hospital through discharge.Engineering and administrative controls as well as PPE and standard operating procedures that are in place in modern BSL-4 laboratories have been associated with a greatly reduced incidence of occupational exposures to infectious agents .12,,Nosocomial transmission of VHF is infrequently described outside of resource-poor settings. With rare exception, such events have occurred because of the lack of recognition that the index patient had such an infection (Yersinia pestis (plague) (Nevertheless, even well-trained HCWs may make mistakes due to anxiety, fatigue, or other stressors, so additional facility enhancements that augment safety are desirable when dealing with potentially lethal infectious diseases. Furthermore, the recognition of a patient with an exotic or unfamiliar contagious disease may engender trepidation among the medical community as well as the public. Such concerns have at times resulted in reluctance on the part of HCWs to care for persons infected with such agents as monkeypox virus (To maximize safety as well as to address provider concerns of HCWs and other staff, we have developed the CIU and our accompanying training program. Our pragmatic and practical approach provides a well-designed facility that enhances safety not only for the care of a patient infected with a laboratory-acquired VHF virus infection, but also for serious transmissible community-acquired disease or for exotic diseases contracted while traveling.Y. pestis (Mycobacterium tuberculosis in Atlanta, Georgia (As international tourism and work assignments continue to expand, the importation of exotic diseases is almost certain to increase and to appear in unexpected locations. Recent instances of infection have occurred with Marburg virus in Colorado (


The aim of this study was to explore the clinical characteristics of and treatment strategies for interstitial pneumonia induced by gefitinib in patients with advanced non-small cell lung cancer (NSCLC). The detailed clinical data of one patient with NSCLC and gefitinib-induced interstitial pneumonia were compiled and a review of relevant previous studies was performed. Based on this case report and the review, the clinical characteristics, mechanisms and treatment strategies of this rare disease were analyzed. The analyses showed that older, male patients with a long smoking history, high smoking index and adenocarcinoma  were more likely to suffer from interstitial pneumonia while taking gefitinib. The onset time of interstitial pneumonia was 1–2 months subsequent to gefitinib administration. The clinical manifestations included chest tightness, shortness of breath, progressive dyspnea, severe hypoxemia and respiratory failure. Diffuse infiltration and alveolar interstitial shadows were observed on the chest tomography scan. In such circumstances, a timely judgment is required, in addition to the withdrawal of gefitinib treatment and the administration of high-dose glucocorticoids, as well as oxygen inhalation and anti-infective therapies, in order to relieve the symptoms. In conclusion, following the onset of gefitinib-induced interstitial pneumonia, the discontinuation of gefitinib is likely to alleviate the suffering of the majority of patients. Early interstitial pneumonia is not an absolute index for the permanent discontinuation of gefitinib treatment. It is necessary to comprehensively consider the benefits and hazards of gefitinib for the patients. Gefitinib, an epidermal growth factor receptor (EGFR) type 1 tyrosine kinase inhibitor, blocks the signal transduction pathway implicated in the proliferation and survival of cancer cells . Phase IA 62-year-old man, complaining of fever and shortness of breath >1 year subsequent to surgery for right-sided NSCLC, was admitted to the First Affiliated Hospital of Xi’an Jiaotong University . In July 2010, the patient was revealed to have a lesion in the right upper lobe of the lung in a physical examination. In August 2010, upper right lobe resection and mediastinal lymph node dissections were performed. The tumor measured 3.5×3.0×2.0 cm. The pathological analysis of the resected upper right lung showed that the patient was suffering from differentiated adenocarcinoma and bronchioloalveolar carcinoma. The lung membrane, bronchial stump and lung hilar lymph nodes were not invaded . Following surgery, the patient did not receive any further treatment. In June 2011, the patient started to cough with obvious incentive; white phlegm was apparent, accompanied by intermittent bloody sputum. A chest computed tomography (CT) scan  showed mFollowing admission, gefitinib administration was discontinued immediately. No evidence of infection or the presence of pathological microorganisms was found in either the sputum or blood culture , while cBased on the case reports and literature reviews on interstitial pneumonia published in Western countries and China between 2003 and 2011, the clinical characteristics of gefitinib-induced interstitial pneumonia were preliminarily analyzed. The results are presented in Gefitinib is an oral selective inhibitor of the EGFR tyrosine kinase and may be effective in patients with advanced non-small-cell lung, ovarian, breast, head and neck or colon cancers. A significant survival benefit has been demonstrated for patients of Asian origin and non-smokers. At present, gefitinib is used as the second or third-line therapy for patients with locally advanced or metastatic NSCLC, following the failure of platinum and docetaxel-based chemotherapies, in a number of eastern Asian countries .The most common adverse effects associated with the use of gefitinib are acneiform skin rashes, diarrhea and nausea, which are usually mild in severity and manageable . HoweverAlthough gefitinib-induced lung injury has a low incidence, the number of patients with gefitinib-induced lung injury is likely to increase. The incidence of ILD during gefitinib treatment varies among different ethnicities. The highest cumulative incidence of 4%, following 12 weeks of gefitinib treatment, was described in a large Japanese cohort of >1,800 patients . In the The clinical manifestations of gefitinib-induced ILD consist of chest tightness, shortness of breath, progressive dyspnea, severe hypoxemia and respiratory failure. Gefitinib-induced ILD may be diagnosed according to previously published and generally accepted clinical criteria . In brieThe patient in this case report was described as being previously healthy, with a long history of smoking and a smoking index of 800. The patient had ceased from smoking for 13 years, and was suffering from bronchioloalveolar carcinoma, which had metastasized to the lungs. Following the failure of the first-line treatments of pemetrexed plus cisplatin, EGFR and K-RAS gene results showed that the patient was suitable for the targeted therapy. One month subsequent to gefitinib treatment, the double-lung metastatic carcinoma was significantly relieved. An analysis of the domestic literature published over the past few years has shown the importance of gender, pathological type and smoking history among the factors affecting response rate and prognosis. Female patients with adenocarcinoma  and no smoking history have a good prognosis and experience an improved quality of life following gefitinib treatment. However, the present case showed that satisfactory efficacy may also be achieved in male patients with adenocarcinoma and a long-term smoking history, providing the results of the genetic testing are in accordance with the indications for gefitinib. This case report indicated that the EGFR mutation status may be the ultimate decisive factor affecting the response rate and prognosis for gefitinib treatment.Adenocarcinoma and individual squamous cell carcinoma have been revealed to be the most common types of gefitinib-induced interstitial pneumonia. A total of 14 case reports of gefitinib-induced interstitial pneumonia that have been published in Western countries were reviewed. These cases each had individual characteristics; however, the majority concerned male smokers with adenocarcinoma. In addition, nine cases of gefitinib-induced interstitial pneumonia were analyzed from the studies published between 2004 and 2011 in China. The patients in these cases shared certain features, such as predominantly being female, with no history of smoking and with adenocarcinoma and a radiation history. These features are correlated with a low risk of ILD occurrence, a high response rate and a long survival. The results of this analysis are consistent with the results of analyses of gefitinib-induced interstitial pneumonia that have been produced in Western countries . The timFollowing treatment, the patient in the present case recovered and continued to take gefitinib under careful medical supervision. The patient was still alive, one year subsequent to the restart of the EGFR tyrosine kinase inhibitor therapy. The outcome of this case showed that the occurrence of controllable ILD is not an absolute index for the discontinuation of gefitinib administration. The benefits to the patient and the risks associated with the use of the drug require comprehensive consideration prior to the decision regarding the continuation or discontinuation of gefitinib therapy being made.Case 18 in In conclusion, when gefitinib is used to treat advanced NSCLC, it confers a high risk of ILD in patients with progression-free survival and a significant clinical benefit in non-smokers, females, patients with adenocarcinoma and patients with no history of thoracic radiotherapy. Gefitinib therapy is an important treatment option for patients with advanced NSCLC; however, physicians should carefully decide on the indications for the use of gefitinib and other cytotoxic agents, particularly for patients with lung comorbidities. In addition, it is necessary for careful attention to be paid to the clinical respiratory symptoms of the patients and the radiographic results, particularly during the first 1–2 months following the initiation of gefitinib treatment.


Aberrant and dysregulated protein glycosylation is a well-established event in the process of oncogenesis and cancer progression. Years of study on the glycobiology of cancer have been focused on the development of clinically viable diagnostic applications of this knowledge. However, for a number of reasons, there has been only sparse and varied success. The causes of this range from technical to biological issues that arise when studying protein glycosylation and attempting to apply it to practical applications. This review focuses on the pitfalls, advances, and future directions to be taken in the development of clinically applicable quantitative assays using glycan moieties from serum-based proteins as analytes. Topics covered include the development and progress of applications of lectins, mass spectrometry, and other technologies towards this purpose. Slowly but surely, novel applications of established and development of new technologies will eventually provide us with the tools to reach the ultimate goal of quantification of the full scope of heterogeneity associated with the glycosylation of biomarker candidate glycoproteins in a clinically applicable fashion. It is a well-established concept that gene expression and protein expression are not the sole factors responsible for phenotype determination. The discovery of the varying roles of post-translational modifications (PTMs) of proteins has identified another level at which functional information is stored. Of the more than 200 different types of protein PTMs, glycosylation is a frequently occurring and particularly important one -4. GlycoSince the initial observation in 1969 showing that membrane glycoproteins of higher molecular weight were present in transformed mouse fibroblasts compared with their normal counterparts ,15, aberSome of the oldest and most common clinically utilized serological biomarkers for cancer diagnosis and monitoring of malignant progression are glycoproteins. Some of these include prominent glycoprotein biomarkers that are widely monitored in patients with prostate cancer (prostate-specific antigen (PSA)), ovarian cancer (carcinoma antigen (CA)125, mucin 16), colon cancer (carcinoembryonic antigen (CEA)), and non-seminomatous testicular carcinoma (human chorionic gonadotropin β-subunit (hCG-β)) , such as the measurement of the core-fucosylated species of AFP in hepatocellular carcinoma ,44. ThisIn the past decade or so, there have been significant advancements in the characterization of the glycosylation patterns of individual proteins and in the identification of glycoproteins in a number of complex biological fluids. This has occurred mostly through the development and refinement of mass spectrometry techniques and equipment, which, when used in concert with the traditional methods used for characterization of protein glycosylation, can provide a powerful complement of tools to tackle the problem of fully understanding the complexity and heterogeneity associated with protein glycosylation and applying the gained knowledge in a clinical setting. However, there has been limited progress in tapping the full potential of glycobiomarkers and their dual nature in order to develop an assay capable of simultaneously delivering information on the absolute quantity of the protein and of its associated glycan structures in complex matrices, such as serum, which is the preferred sample type for high-throughput clinical analysis.Some of the best and most widely recognized cancer biomarkers are highly tissue-specific, such as PSA for prostate tissue, hCG for the placenta, and AFP for the developing fetus Figure . Using sHowever, there is a series of technical and biological obstacles to developing quantitative assays that reflect the full picture of the status of a glycoprotein biomarker. The majority of challenges preventing reliable, clinically applicable binary measurement of glycoprotein biomarkers are of a technical nature. More specifically, there is only a very limited set of tools capable of performing this task, each with its own set of associated limitations and difficulties. Currently, the options for concurrent quantification of a protein and its associated glycans are limited to a combination of antibody-mediated protein capture and detection with glycan-specific antibodies, lectins, or mass spectrometry. The advancement of these approaches is hindered by the absence of a suitable recombinant technology capable of reliable and convenient production of glycoproteins with the desired glycan structures, which would allow for more convenient and detailed studies. However, because protein glycosylation is not a template-driven linear sequence-based process, such as DNA or protein synthesis, a suitable solution to this problem does not seem to be on the horizon, even though some advancements have been made . Owing tThe majority of the top 22 high-abundance plasma proteins, which account for 99% of protein content in serum, are glycoproteins . These iTherefore, in this review, we focus on the technologies with the capability or a strong potential for binary (protein and carbohydrate) measurement of glycoprotein cancer biomarkers in serum, and describe the challenges associated with the different approaches.The existence of lectins has been known for over 100 years, since the discovery of ricin by Stillmark in 1888 . HoweverEnzyme-linked lectin approaches for detection of carbohydrates have been known and used for close to 3 decades ,52. ThesIt must be noted that the antibody-lectin sandwich approaches are plagued by a number of technical issues, which can be addressed with varying degrees of success. A major issue is the inherent glycosylation of the antibodies used to capture a specific glycoprotein, which can cause a non-specific background signal from lectin binding, often masking the signal from the glycoprotein of interest. This effect can be minimized by the enzymatic or chemical derivatization of the antibody-associated carbohydrates prior to use in the assay ,64,65. ALens culinaris agglutinin (LCA)-reactive species of alpha-fetoprotein (AFP-L3). This has been shown to improve the specificity for hepatocellular carcinoma (HCC) compared with total AFP levels, as the latter can be elevated in pregnancy, hepatitis, and liver cirrhosis . S. Set al.a antigen on glycoproteins and glycolipids, and is used for monitoring of pancreatic cancer progression and recurrence, and for differentiation of the cancer from pancreatitis [Although lectin and MS-based approaches for quantification of glycoproteins are the most common, there are other technologies that are also applied, and new ones are being developed, to be used alone, or in combination with each other. Well-established liquid-chromatography techniques using HILIC or PGC are readily available for enrichment and separation of glycan and glycoconjugates in conjunction with other detection and quantification methods -118. Thereatitis ,121,122.reatitis ,124.in vitro systems, and will require further testing before application in a clinical setting.Chromatography-based strategies have also been used with some success. Ion-exchange chromatography is being used clinically for separation and quantification of serum transferrin glycoforms to test for congenital disorders of glycosylation ,126. KLKThe clinical potential of glycoprotein biomarkers in cancer is indisputable. Some valuable successes have been achieved in the field, yet there is much room for improvement. The majority of the tools currently available have proven their utility beyond doubt when used for qualitative and characterization purposes. However, for each of these technologies, the leap from analytical to quantitative applications has not been sufficiently successful.Over the next decade, the major goal will be the reliable detection and quantification of the full scope of glycan heterogeneity on any particular glycoprotein of interest, and the ability to differentiate these patterns between homeostatic and disease conditions. When the recent literature is searched for 'glycosylation quantification', it quickly becomes obvious that MS-based approaches have almost become an absolute requirement. However, when viewing the field as a whole, one gets an appreciation of the fact that MS advancements alone will not bring a major breakthrough. In the near future, the development of even more new glycan-recognition agents can be expected, such as novel naturally occurring or recombinant lectins, carbohydrate-recognizing antibodies, aptamers, and other glycobiosensors. Progress is also being made in the engineering and synthetic production of protein glycosylation, which will greatly aid in the creation of standards and uniform model systems for development of precise quantitative assays. In the near future, the predominance and expansion of immuno-based and lectin-based methods in practical applications of glycan quantification can be expected, especially given the recent advances in microarray technology. We believe that MS holds the greatest potential, but it is still hampered by a number of technical limitations, which will require significant technological progress to be made before it will be sufficiently reliable and applicable in the most appropriate manner. Nonetheless, we believe that MS is the most promising tool for detection and quantification of the full scope of protein-associated glycosylation down to the single monosaccharide unit level. The future appears bright, and progress in the field is inevitable; the only uncertainty is how long it will take.AFP: alpha-fetoprotein; CA: carcinoma antigen; CEA: carcinoembryonic antigen; ELISA: enzyme-linked immunosorbent assay; ELLA: enzyme-linked lectinsorbent assay; hCG: human chorionic gonadotropin; MRM: multiple reaction monitoring; PSA: prostate-specific antigen; PTM: post-translational modification; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; SRM: selected reaction monitoringThe authors declare that they have no competing interests.UK conceived and wrote the majority of the review. HK assisted in the development of the manuscript and wrote a part of the review dealing with MRM-based quantification of glycopeptides. EPD provided support and supervision throughout the development of the review. All authors have read and approved the manuscript for publication.At the time of submission of the manuscript, Uros Kuzmanov was a PhD student in the laboratory of Dr Eleftherios P. Diamandis, Professor of Laboratory Medicine and Pathobiology at the University of Toronto. Dr Hari Kosanam is a postdoctoral fellow in the same laboratory.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/31/prepub


Giorgio Cometto and colleagues discuss the study by Tankwanchi and colleagues on physician migration to the United States from sub-Saharan Africa and the steps that the US, other destination countries, and SSA countries can take to address the problem.Please see later in the article for the Editors' Summary Migration of health workers from low- and middle-income countries (LMICs) to high-income countries is one of the most controversial aspects of globalization, having attracted considerable attention in the health policy discourse at both the technical and political level Four countries  together employ 72% of foreign-born nurses and 69% of doctors working in the Organisation for Economic Co-operation and Development PLOS Medicine, a new analysis of physician migration from sub-Saharan Africa (SSA) to the United States by Tankwanchi and colleagues (OECD) bloc The WHO Code represents an unprecedented opportunity for countries to collaborate on tackling the negative effects of HRH migration. In addition to the migration-specific measures , the Code recognizes the interconnectedness of HRH actions in the national and global health labor markets, and the need for a systemic approach to health workforce development, recommending that countries should aim towards self-sufficiency in HRH production, and put in place the regulation, education, and management policies, and incentives to enhance retention.Adopting effective policies to address international health workforce migration requires both understanding the local drivers of (inward or outward) migration, as well as identifying evidence-based policy options. In the case of the US, challenges include chronic under-investment in physician training and a failure to select trainees from under-served areas; additionally, licensing creep for some fields translates into higher training costs and educational debt loads, resulting in higher wage demands and a reluctance by US-trained health workers to serve in low-income areas Recurrent problems that affect most SSA countries include under-investment in HRH education, inadequate attention to supportive management practices, limited opportunities for career progression and professional development, and poor remuneration and incentives Of course, denouncing the negative effects of international HRH migration and identifying its root causes are not enough; shifting to a problem-solving mode requires identifying and putting in place effective solutions. With regard to destination countries, experience from the UK shows that ethical guidance alone was ineffective in preventing inflow of doctors between 2001 and 2004, due to competing priorities of the NHS. Only when the UK increased domestic training numbers, changed immigration laws, and introduced bilateral agreements with source countries did new registrations of overseas physicians decline drastically  Some source countries are also taking action: facing a dramatic shortfall of health workers in the early 2000s, Malawi implemented an Emergency Human Resources Programme (EHRP), which boosted domestic training of health workers and facilitated in-country retention through a variety of measures, including a 52% salary top-up for priority cadres, and an expansion of opportunities for post-graduate training. Between 2004 and 2009, the EHRP increased the number of health care workers by 53%, raising the HRH density from 0.87 to 1.44/1,000 population Simply increasing the wages of physicians in LMICs is not effective, as many more factors such as working conditions, housing, and career advancement play a role in their departure. The current nurse and midwife strike in Liberia For most LMICs, matching the levels of remuneration and the opportunities for specialized training and research available in advanced economies is not realistic in the short-term, nor is it desirable given the competing needs for use of limited public resources. A recent literature review has identified realistic strategies of proven effectiveness to limit the negative effects of HRH migration on LMIC placing greater emphasis on non-wage retention strategies, including improving working and living conditions diversifying the skills mix to harness the potential of non-physician clinicians circular migration, i.e., promoting a triangular flow of talent and skills by encouraging some migrant health workers to return to their home country In parallel, OECD countries could decrease their reliance on foreign-trained health workers by:increasing investment in domestic health professional education and aligning government educational spending with employment opportunities. For example, an analysis showed that the US had 116,000 nursing vacancies piloting or expanding innovative financing mechanisms, for instance allowing local and private entities to provide complementary funding to the (US) federal government's National Health Service Corps, a bonding system whereby physicians receive scholarships or educational loan repayment in exchange for guaranteed service in underserved communities;not hiring from the countries with the worst health care worker-to-population ratios;adopting a shared regulation approach  to health professional schools and health professions, which are now entirely self-regulated;encouraging the development of more cost-effective ways to educate health professionals through innovation grants;planning a more diversified skill mix for the health team, better harnessing the complementarity of different cadres, including nurse practitioners, physician assistants, medical assistants, and primary care emergency medical technicians The upcoming Third Global Forum on Human Resources for Health, to be held in Recife, Brazil, on 10–13 November 2013, will provide an opportunity to commit to the policy and investment decisions that need to be adopted for a sustainable and systemic strengthening of the health workforce, as a critical element in the drive towards universal health coverage


Stimulation of mitochondrial biogenesis during life-time challenges both eliminates disadvantageous properties and drives adaptive selection of advantageous phenotypic variations. Intermittent fission and fusion of mitochondria provide specific targets for health promotion by brief temporal stressors, interspersed with periods of recovery and biogenesis. For mitochondria, the mechanisms of selection, variability, and heritability, are complicated by interaction of two independent genomes, including the multiple copies of DNA in each mitochondrion, as well as the shared nuclear genome of each cell. The mechanisms of stress-induced fission, followed by recovery-induced fusion and biogenesis, drive the improvement of mitochondrial functions, not only as directed by genotypic variations, but also as enabled by phenotypic diversity. Selective adaptation may explain unresolved aspects of aging, including the health effects of exercise, hypoxic and poisonous preconditioning, and tissue-specific mitochondrial differences. We propose that intermittent purposeful enhancement of mitochondrial biogenesis by stressful episodes with subsequent recovery paradoxically promotes adaptive mitochondrial health and continued healthy aging. Convention holds that mitochondrial gene variability (heteroplasmy) is detrimental to organisms . Because of the interaction, mitochondria are subject to complex selection, ranging from genetic selection of heteroplasmic variants to the epigenetic environment in which the mitochondria pass through multiple generational cycles. Epigenetics allows a cell or network to store the effects of experiences and modify the decoding of the genome. Depending on the unit, epigenetic memories are stored as methylation, altered microRNA profiles, nucleosome positions, or chromatin alterations in the case of nDNA. Epigenetic imprints can be transferred to offspring units and passed to subsequent generations in eukaryotes , close to 6  mitochondria to a large degree (Khrapko et al., Findings from bacteria show that clonal populations may exhibit cell-to-cell variation in response to stress. Very recent findings show that variability persists through cell division events, and that epigenetic inheritance contributes to the propagation of the observed phenotypic variation (Ni et al., Studies on mtDNA mutator knock-in mice, a model for premature aging due to somatic mitochondrial damages, show that 5 months of endurance exercise rescues the progeroid phenotype and induces dramatic systemic mitochondrial rejuvenation, including fewer mitochondria with damaged DNA (Safdar et al., When brain energy turnover increasingly depends on ketone body or fatty acid metabolism rather than on glucose, sparing of complex I and proliferation of mitochondria is beneficial to overall mitochondrial health.High glucose availability for oxidative phosphorylation, on the other hand, establishes a state of low selection pressure with increased accumulation of lesions.Intermittent non-chronic insults with increased ROS production benefit mitochondrial health and promote healthy aging and increased longevity.In healthy tissue, transient non-lethal insults such as chemotherapy, hypoglycemia, or hypoxic challenges, select mitochondria that are more resilient to subsequent challenges. These mitochondria are better adapted and more numerous.Stressful challenges with increased ROS levels, followed by subsequent recovery and treatment with biogenesis-promoting agents, yield mitochondria with greater respiratory capacity than mitochondria treated with biogenesis-promoting agents alone.This perspective deals with the notion that adaptive stress responses to respiratory challenges and stimulation drive natural selection of genetically and epigenetically inherited properties of mitochondria:These claims have specific and testable implications, the resolution of which can revise the general understanding of the role of mitochondrial challenges in healthy aging.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In addition to genetic makeup, age, and gender, our diet has a major impact on the immune status and the intestinal microbiota. In return, alterations in the latter and their metabolites affect both local and systemic immunity. The microbiota and diet contribute important substrates, enabling the generation of essential compounds like vitamins that support the biosynthesis of many products throughout the body. As such, the diet constitutes a major contributor to the composition and maintenance of cells of the immune system and health status of the host. Immune protection against invading microorganisms and their products is often initiated at epithelial barrier sites such as the intestine. At these sites reside specialised lymphocytes that are important not only as a first line of defence but also in epithelial barrier organisation and wound repair.The transcription factor aryl hydrocarbon receptor (AhR) is selectively expressed in some immune cells, importantly in Th17, gamma/delta T cells and innate lymphoid cells. All these cell types are found, and often enriched, at barrier sites. The AhR contains a paired Per-Arnt-Sim (PAS) domain, highly conserved in proteins involved in sensing environmental change. Its activation is important for optimal development of the Th17 cell subset and results in enhanced activation of both Th17 and IL-17 producing gamma/delta T cells and their capacity to produce IL-22. Especially at epithelial sites, AhR activation in response to endogenous and exogenous ligands may constitute a way in which environmental stimuli could affect the immune status. Surprisingly, we found that elements from the diet are responsible for the activation of AhR in intestinal immune cells.


Chronic kidney disease (CKD) comprises a group of pathologies in which the renal excretory function is chronically compromised. Most, but not all, forms of CKD are progressive and irreversible, pathological syndromes that start silently , continue through renal dysfunction and ends up in renal failure. At this point, kidney transplant or dialysis  becomes necessary to prevent death derived from the inability of the kidneys to cleanse the blood and achieve hydroelectrolytic balance. Worldwide, nearly 1.5 million people need RRT, and the incidence of CKD has increased significantly over the last decades. Diabetes and hypertension are among the leading causes of end stage renal disease, although autoimmunity, renal atherosclerosis, certain infections, drugs and toxins, obstruction of the urinary tract, genetic alterations, and other insults may initiate the disease by damaging the glomerular, tubular, vascular or interstitial compartments of the kidneys. In all cases, CKD eventually compromises all these structures and gives rise to a similar phenotype regardless of etiology. This review describes with an integrative approach the pathophysiological process of tubulointerstitial, glomerular and renovascular diseases, and makes emphasis on the key cellular and molecular events involved. It further analyses the key mechanisms leading to a merging phenotype and pathophysiological scenario as etiologically distinct diseases progress. Finally clinical implications and future experimental and therapeutic perspectives are discussed. Chronic kidney disease (CKD) comprises a group of pathologies in which the renal excretory function is chronically compromised, mainly resulting from damage to renal structures. Most, but not all, forms of CKD are irreversible and progressive. Renal damage includes (i) nephron loss due to glomerular or tubule cell deletion, (ii) fibrosis affecting both the glomeruli and the tubules, and (iii) renal vasculature alterations. CKD results from a variety of causes such as diabetes, hypertension, nephritis, inflammatory and infiltrative diseases, renal and systemic infections , polycystic kidney disease, autoimmune diseases (e.g. systemic lupus erythematosus), renal hypoxia, trauma, nephrolithiasis and obstruction of the lower urinary ways, chemical toxicity and others. In a variable number of cases, renal injury by any of these causes evolves towards a chronic, progressive and irreversible stage of increasing damage and renal dysfunction wherein, eventually, renal replacement therapy  becomes necessary ,2.Whether started as glomerular, tubular or renovascular damage, chronic progression eventually converges into common renal histological and functional alterations affecting most renal structures, which lead to progressive and generalized fibrosis and glomerulosclerosis. Once initiated, kidney injury gradually aggravates even in the absence of the triggering insult. Congruently with a common chronic phenotype, CKD can be diagnosed independently from the knowledge of its cause. The National Kidney Foundation (NKF) of the United States of America classifies CKD progression in five stages according to the extent of renal dysfunction and renal damage, symptomatology and therapeutic guidelines table . Late stThe term uremia or uremic syndrome refers to the clinical manifestations of CKD, which are derived from the inability of the kidneys to properly clear the blood of waste products. As a consequence, toxic substances usually eliminated through the urine become concentrated in the blood and cause progressive dysfunction of many  other tissues and organs, seriously compromising well-being, quality of life and survival. For example, elevated serum uric acid is a marker for decreased renal function, may have a mechanistic role in the incidence and progression of renal functional decline ,8. In a A representation of GFR evolution in time is a helpful estimation of renal disease progression rate. It is useful to monitor CKD as well as to predict the time for RRT. Progression rate is highly dependent on the underlying cause but, due to genetic heterogeneity, it is also very variable among subjects with the same etiology . In geneThe key and yet unmet issue in CKD is why, and through which mechanisms, persistence of triggering damage or repetitive bouts, initially repairable as in acute damage events, eventually go beyond a no return point, after which non reversible chronicity ensues. The responses to these questions are beyond our present knowledge of CKD pathology. The development of early diagnostic and prognosis markers, and effective, curative -not merely palliative or delaying- therapies critically depend on our finding answers to these largely ignored questions. Notwithstanding, knowledge has emerged in the last few decades on new mechanisms and molecular pathways that mediate the development of certain facets of chronic phenotypes. This knowledge is potentially useful for optimizing current therapies and for developing new ones. The purpose of this review is to describe the pathophysiological processes leading to tubular, interstitial, glomerular and renovascular chronic diseases, focused on the cellular and molecular mechanisms involved, making emphasis in those that are common for most CKDs regardless of aetiology.A variety of renal injuries may eventually evolve to CKD . DiseaseSome decades ago, the leading cause of CKD was glomerulonephritis secondary to infections. Antibiotics and improved sanitary conditions have laid the way to diabetes and hypertension as the first and second leading causes of end stage renal disease (ESRD) in the developed world, respectively . In factA genetic predisposition for renal failure is demonstrated by the 3-9 times higher probability of ESRD in patients with a family history of CKD, compared to the general population . HoweverExcept for monogenic diseases  , geneticGenetic analysis of renal damage-prone rats crossed with more resistant strains have revealed the existence of 15 loci associated with renal disease , three oThe terms tubular diseases, tubulointerstitial diseases, tubulointerstitial nephritis and tubulointerstitial nephropathies refer to a heterogeneous panel of alterations which primarily affect both cortical and medullary tubules and the interstitium, and secondarily other renal structures such as the glomeruli . TubulesIndependently of the triggering cause, characteristic hallmarks of tubulointerstitial diseases are tubular atrophy, interstitial fibrosis and cell infiltration , resultiTubulointerstitial diseases can be considered as perpetuating inflammatory responses that escape normal defense and restorative mechanisms . The immAs a consequence of the damage inflicted to tubular structures by the triggering insult, an initially restorative response starts, which eventually corrupts into a pathological vicious cycle of interstitial fibrosis and tissue destruction. Depending on the insult, tubular epithelial cell necrosis, apoptosis, or both are observed. In a restorative effort, an inflammatory response is implemented and tubular cells proliferate to substitute for dead cells. For unknown reasons, under undetermined circumstances the restorative process (in this and the next phases -see below-) loses the appropriate regulation and takes an irreversible self-destructive course that does not need the presence of the initial insult to progress. Interstitial fibrosis results from a deregulated process of fibrogenesis initially required to rebuild the normal tissue structure posed by ECM and basement membranes . Rather Tubular epithelial cells respond to the initial insult by (i) proliferating or (ii) dedifferentiating through an epithelial to mesenchymal transition (EMT)-like process that allows them to migrate, proliferate and eventually redifferentiate ,58. EMT Infiltrated cells, spanning the endothelium of peritubular capillaries , or prolDamage also activates renal fibroblasts, which proliferate and constitute an important source of pathological, fibrogenic ECM components, such as collagens and fibronectin ,61,75,76In most forms of CKD, the number of interstitial myofibroblasts is increased, and strongly correlates with the degree of interstitial fibrosis ,78. ActiUnder pathological conditions during CKDs, damaged renal tissue is replaced by a scar-like formation, characterized by excessive ECM accumulation and progressive renal fibrosis. Fibrosis is the consequence of (i) an increased synthesis and release of matrix proteins from tubular cells, fibroblasts and mostly myofibroblasts, and (ii) a decreased degradation of ECM components ,88. Duride novo synthesized proteins  . EvIncreased production of ROS in pathological situations such as hypertension and atherosclerosis is frequently mediated by activation of the renin-angiotensin system and NAD(P)H oxidase -213. As Severe occlusions decreasing over a 60% of renal flow, lead to a reduction of renal perfusion pressure under the autoregulatory range (< 70-85 mmHg). Renal hypoperfusion appears only when renal perfusion pressure falls below the autoregulatory range, and thus renal blood flow declines. It is estimated that a 70-80% of the luminal area of the renal artery must be occluded for hypoperfusion to occur, which is termed "critical stenosis" . This co2 and glucose supply limit ATP production, which leads or predisposes cells to dying [Severe renal hypoperfusion leads to microvascular rarefaction (MR) and deficient vascular endothelium growth factor (VEGF) production and focal or spread ischemia . MR seemto dying -226. Hypto dying .Hypertension is a prospective inducer of renal damage in stenotic kidneys . HyperteRenal artery stenosis may affect one kidney or both, which induces different pathological scenarios figure . The casIn unilateral stenosis, the obstructed kidney responds as in bilateral stenosis with renin release, angiotensin II production and hypertension. In unilateral stenosis, maintenance of hypertension is dependent on a constantly activated RAS. High levels of circulating and renal angiotensin II become increased , which pIrrespective of the cause, CKD pathogenesis is characterized by a progressive loss of renal function, and an excessive deposition of extracellular matrix in the glomeruli and tubular interstitium . CKD proMechanisms traditionally suggested to connect primary glomerulopathies with the subsequent pathological recruitment of the tubulointerstitial space are : (i) an Regardless of cause, as a consequence of the increasing renal dysfunction, compensatory responses are activated, which may also engage in the progressive pathological vortex. These responses include hypertension and peripheral or renal sympathetic hyperactivity , which aThis review summarizes the key pathophysiological events of CKDs compromising renal excretory function, at the organism, tissue, cell and molecular levels. CKDs may be originated in the glomeruli, in the tubuli or in the renal vessels. Most of the diseases in each of these groups have specific, but also common pathophysiological characteristics resulting from increasingly understood mechanisms of action. Moreover, all these diseases, regardless of aetiology, eventually affect all parts of the nephron and enter an irreversible course that may compromise the patient's life. In addition, as the disease progresses, a more uniform pathophysiological pattern installs characterized by increasing fibrosis, inflammation, nephron loss and parenchymal scarring. Present treatments of CKD are only reasonably effective at slowing progression. They are installed substantially after irreversibility ensues, mostly because clear pathological signs only arise after over 50% of the nephrons are functionally nulled. In these conditions, the earliest possible diagnosis is critical for prognosis. Moreover, the identification of new biomarkers and technologies to move progressively earlier the moment of diagnosis is an active area of research.The follow-up of CKD patients shows that the overall death rate increases as kidney function decreases, and the mortality in patients with ESRD remains 10-20 times higher than that in the general population. At present there is no cure for CKD; the natural course of the disease is to progress towards ESRD and death, unless dialysis or transplant is implemented. The focus in recent years has thus shifted to optimizing the care of these patients during the phase of CKD, and to slow progression with the aim of avoiding the necessity of renal replacement therapy during the patient's lifespan. In many cases, it is possible to slow the progression of CKD to ESRD if kidney disease is diagnosed and treated in its earlier stages, mainly with renin-angiotensin system blockers, although other drugs are under development based on known mechanisms of progression ,249. ThuYet, a valuable and potentially useful piece of knowledge for the clinical handling of CKD is still in the horizon; namely understanding how and why an initial or persistent insult to the kidney is not repaired but, on the contrary, leads to an irreversible scenario of self destruction, which even becomes independent from the cause. This no-return point in the fate of injured kidneys probably holds the key to a conceptual therapeutic drift from slowing progression towards regression and, along with a sufficiently early diagnosis, prevention entering the vicious circle of deterioration. As it has been suggested that an imbalance of pro-fibrotic and anti-fibrotic cytokines is in the core of the no-return point , it woulThe authors declare that they have no competing interests.JML-N drafted the manuscript and contributed with specific information and critical analysis through the manuscript. ABR-P provided most of the information on tubulointerstitial diseases. AO introduced the clinical scope to the manuscript and specific aspects of sections 1 and 2.3. CM-S incorporated a part of the information in sections 3 and 4, provided specific pieces of information through the manuscript and critically helped with the draft. FJL-H delineated and wrote most of the manuscript, composed the figures and integrated the information into sections 5 and 6. All authors read and approved the final manuscript.


Since 1998, the Eastern Democratic Republic of the Congo has been torn by a military conflict. A particular atrocity of the war is widespread sexual violence.In this combined retrospective analysis and prospective survey, we sought to identify hospital facilities and resources available to treat victims of sexual violence in Goma, the capital city of the North Kivu province.Of twenty-three acute care hospitals registered in the area of Goma, four (17%) regularly cared for victims of sexual violence. One hospital had all resources always available to appropriately care for victims of sexual violence. From Jan 2009 until Oct 2010, 7,048 females sought medical care because of physical or psychological sequelae from sexual violence in the four hospitals of Goma. Only half of the hospitals had physicians specialized in gynaecology or gynaecological surgery available. Similarly, anaesthetists and psychiatrists/psychologists were available in two (50%) and one (25%) hospital, respectively. Post-discharge care facilities, material resources, such as surgical and anaesthesiological equipment and drugs, were inconsistently available in the hospitals caring for sexually abused females. At one selected hospital, acyclovir and/or antibiotics were administered to 1,202 sexually abused females (89.5%), whereas post-exposure HIV prophylaxis and surgery because of vesico-vaginal fistula was provided to only 75 (5.6%) and 121 (9%) patients, respectively.This study provides data that only few hospitals in Goma care for victims of sexual violence. In addition, these hospitals suffer from a relevant shortage of human and material resources to provide adequate care for sexually abused females. Aside from establishment of adequate protection strategies, steps must be taken to increase the availability of trained health care professionals and resources to provide adequate care for victims of sexual violence in Goma and the North Kivu province. Since 1998, the Eastern Democratic Republic of the Congo has been torn by a military conflict characterized by extreme violence, mass population displacements and a collapse of public health services . A partiWhile the latter survey studied the situation in the South Kivu province, a high prevalence of sexual violence has been reported in the North Kivu province, too ,4. Just In this study, we sought to identify hospital facilities and resources available to treat victims of sexual violence in the area of Goma, which is the capital city of the North Kivu province in the Eastern Democratic Republic of the Congo.This analysis was designed as a combined retrospective study and prospective survey. It was performed in the city of Goma and the DOCS Hospital, which is a 40-bed, non-governmental organization-run hospital located in Goma. The study protocol was approved by the Ethics Committee of the Medical University of Goma. Since no direct patient data were retrieved and hospitals were free to present data, written informed consent was waived.Our study evaluated the time period from Jan 2009 until Oct 2010 and had three main objectives: (1) assessment of the number of victims of sexual violence seeking medical care in the hospitals of Goma; (2) assessment of the availability of key resources to treat victims of sexual violence in hospitals regularly caring for victims of sexual violence; and (3) assessment of the frequency of delivery of three indicator treatments  to victims of sexual violence at the DOCS Hospital in Goma.Our survey evaluated all acute care hospitals located in the area of Goma. According to the local health care office, hospitals are defined as health care institutions running at least 20 beds. The medical director or the person specifically dedicated to the care of sexually abused females at these hospitals was contacted and asked whether victims of sexual violence were regularly (at least one victim per week) cared for. If persons contacted at each hospital stated that the hospital regularly cared for patients following sexual violence, these institutions were visited and included in the survey. During on-site visits consisting of personal interviews and visits of key hospital facilities , the number of patients admitted because of physical or psychological sequelae of sexual violence during the observation period was retrieved. Furthermore, data on the following resources were collected using a predefined systematic protocol: number of beds, administrative background, availability of a physician specialized in gynaecological surgery or gynaecology, anaesthetist, psychiatrist or psychologist, post-discharge medical services, laboratory tests to diagnose pregnancy and sexually transmitted diseases , instruments for gynaecological examination, acyclovir, chinolone and/or tetracycline antibiotics, post-exposure HIV prophylaxis, operation room, instruments for basic wound care, instruments to perform gynaecological surgery, basic surgical and anaesthetic resources including an autoclave, suction machine, electric cautery, oxygen, vaporizer to deliver inhalational narcotics, patient monitor measuring at least plethysmographic oxygen saturation, materials to administer neuro-axial anaesthesia, and materials for airway management. Availability of drugs (including expiry dates), laboratory tests (including expiry dates), instruments, surgical and anaesthetic resources was documented as 'always', 'sometimes', or 'never'. Selection of these resources was based on recommendations to manage sexually violated females as published by the United Nations Population Fund (UNFPA) and the United Nations International Children's Emergency Fund (UNICEF), as well as practical experience of the authors.The DOCS hospital, which is supported by the non-governmental organization 'Doctors on Call for Service', was the first hospital in Goma to care for women following sexual violence. The reason for this was the availability of a specialist surgeon providing surgical care for sexually violated women . Over the years, apart from orthopaedic surgery, the DOCS hospital specialized in caring for sexually abused women. The reason why the DOCS hospital was singled out as an exemplary hospital to provide data on the medical course of the patient in this study is the fact that statistical data on the detailed medical management of women after sexual violence could not be retrieved from other hospitals.The following data were collected from medical records and the administrative register of the DOCS hospital using a standardized protocol: total number of hospital admissions, number of patients admitted following sexual violence, and percentage of sexually abused patients receiving one of the following treatments: acyclovir and/or antibiotics for sexually transmitted diseases, post-exposure HIV prophylaxis, and/or vesico-vaginal fistula repair surgery. Data were collected for the period from Jan 2009 until Oct 2010.Statistical analyses were performed using the SPSS 13.0.1 software package . Descriptive methods were used to present data. Variables are presented as median with minimum and maximum values, if not otherwise indicated.n = 5; non-governmental organization, n = 5; mission, n = 10; private, n = 3) and which met our inclusion criteria and were contacted, four (17%) stated to regularly care for victims of sexual violence and were visited for further data documentation. One hospital had all resources always available to appropriately care for victims of sexual violence. During the observation period, 7,048 females sought medical care because of physical or psychological sequelae from sexual violence in the four surveyed hospitals , post-exposure HIV prophylaxis , and surgery because of vesico-vaginal fistula .From Jan 2009 until Oct 2010, 4,796 patients were admitted to the DOCS hospital. One-thousand-three-hundred-forty-three (28%) patients were admitted because of physical or psychological sequelae following sexual violence. Percentages of patients who received one of the three evaluated specific treatments were as follows: administration of acyclovir and/or antibiotics for sexually transmitted diseases , to provide care for sexually abused women at these institutions. Over the years, apart from other medical fields, these institutions evolved as specialized centers to provide care for victims of sexual violence in Goma. Finally, the local health care authorities selected the four institutions as referral centers for the care of sexually abused females.e.g. surgical and anaesthesiological equipment, drugs) poses a relevant barrier to adequate care of victims of sexual violence. The only exception is chinolone and tetracycline antibiotics as well as HIV tests which were reported to be consistently available in all hospitals.Shortages of resources to care for victims of sexual violence in the few Goma hospitals appear multifaceted. On the one hand, there is an obvious lack of adequately trained health care providers, such as physicians able to perform gynaecological surgery, anaesthetists, and psychiatrists or psychologists, to care for sexually abused females in- and outside the hospital. Our results regarding inconsistencies in post-discharge care of sexually abused females are in line with the findings of the United Nations panel reporting unmet needs of victims of sexual violence, particularly in remote areas . The lacSelected data from the DOCS Hospital suggest that the majority of females following sexual violence receive acyclovir or antibiotics to treat or prevent sexually transmitted diseases. In contrast, administration of post-exposure HIV prophylaxis was very low. Given the high prevalence of HIV infection among African soldiers , prescrie.g. the Rutshuru, Lubero, Masisi, and Walikale regions) since Nov 2009 . Considering that many victims of sexual violence never seek medical care and that some who seek medical care do so at smaller hospitals or clinics outside of Goma, our survey has the potential to relevantly underestimate the burden of sexually abused females in Goma. The fact that some females do not present to medical institutions at all while others present only with a relevant delay may diminish the benefit of sufficient human and material resource availability to provide medical care for sexually abused women. Aside from functioning referral systems and transportation facilities, educational campaigns are needed to inform victims about the time sensitivity of post-rape care.The low number of hospitals caring for victims of sexual violence together with the lack of human and material resources has resulted in a substantial impediment to medical care provided to sexually abused females in the North Kivu province. Currently, it is estimated that approximately 1,000 women and girls are waiting for medical care following sexual violence in rural territories around Goma (Our study carries several limitations. First, the study was not piloted, and resources considered necessary to care for sexually abused females in this study have not been validated or shown to improve the care and outcome of victims of sexual violence. In accordance with international recommendations and practical experience of the authors, these materials were regarded as indispensable to provide adequate patient care. Second, considering the small sample size of surveyed hopitals, our results must not be extrapolated to other areas of the North Kivu province or Democratic Republic of the Congo. Since the hospitals in Goma are referral hospitals for the North Kivu province, it is, however, likely that medical facilities and resources to provide care for victims of sexual violence are even more limited in remote areas of the region. Third, our study evaluated only three indicator medical therapies provided to victims of sexual violence at a selected hospital and did not comprehensively evaluate the medical care provided to sexually abused females in Goma. This weakens the conclusion of our study that resource restraints substantially affect the quality of patient care. Finally, it is noteworthy that not all information collected during interviews could be verified during on-site visits of the study hospitals.This study provides data that only few acute care hospitals in Goma care for victims of sexual violence. In addition, these hospitals suffer from a relevant shortage of human and material resources to provide adequate care for sexually abused females. Aside from establishment of adequate protection strategies, steps must be taken to increase the availability of trained health care professionals and resources to provide adequate care for victims of sexual violence in Goma and the North Kivu province.DOCS: Doctors on Call for Service; HIV: Human immunodeficiency virus; UNFPA: United Nations Population Fund; UNICEF: United Nations International Children's Emergency FundThe authors declare that they have no competing interests.IB designed the study, conducted the on-site survey, critically revised the manuscript for important intellectual content and gave final approval of the version to be published. MWD designed the study, drafted the manuscript and gave final approval of the version to be published.


Celiac disease is a T-cell mediated chronic inflammatory disorder with an autoimmune component. Altered processing by intraluminal enzymes, changes in intestinal permeability, and activation of innate immunity mechanisms seems to precede the activation of the adaptive response. Significant progress has been made in the understanding of the cellular and molecular basis of CD and in the consequent identification of potential targets for therapy. Recently, it has been shown that gliadin peptides are highly resistant to digestive processing by pancreatic and brush border proteases. Enzyme supplement therapy using bacterial prolyl endopeptidases has been proposed to destroy T-cell multipotent epitopes. The identification of T-cell stimulatory gliadin sequences is important. Breeding programs and/or transgenic technology may lead to production of wheat that is devoid of biologically active peptide sequences. The identification of specific epitopes may also provide a target for immunomodulation of antigenic peptides. Other promising areas include preventing gliadin presentation to T cells by blocking HLA binding sites, use of tTG inhibitors, and assessing IL-10 as a tool for promoting tolerance. However, evidence that gluten toxicity is not dependent only on T-cell recognition is growing; activation of innate immunity has been demonstrated and antibodies to IL-15 proposed, particularly in refractory sprue because of the IEL activating role of IL-15. However, one should realize that CD is a benign disease and dietary treatment is safe, although strenuous An immunomodulatory approach will need to have a safety profile equivalent to that of the GFD, but with the advantage of increased compliance. Another area of important changes for CD concerns the diagnostic protocol. In 1990 ESPGHAN has revised its former diagnostic criteria laid down in 1970. The two requirements mandatory for the diagnosis of celiac disease (CD) remain: 1) the finding of villous atrophy with hyperplasia of the crypts and abnormal surface epithelium, while the patient is eating adequate amounts of gluten; and 2) a full clinical remission after withdrawal of gluten from the diet. However, important changes that might have an impact on the diagnostic procedures for CD, have occurred in recent years. Tests based on the detection of anti-endomysium antibodies (EMA), and subsequently of anti-tTG, have been increasingly used as an initial screen for CD. Serological tests are largely responsible for the recognition that CD is not a rare disease; moreover, with the notion of the relatively high prevalence of CD has become increasingly recognised its broad spectrum of clinical presentations. The growing contribution of serology, together with the recognition of a wider spectrum of histological changes (see below), and the contribution by genetic tests, demonstrate the necessity to move on to a revised diagnostic approach, but until serological methods are improved, the genetic make up of celiac patients is better defined, it seems wise for a diagnosis of celiac disease still rely on a combined approach based of clinical criteria, histology, serology and genetics.


Thus far, molecular and cellular pathways of disease progression are largely unknown. One of the key players in this destructive scenario are synovial fibroblasts (SF) which actively attach to, invade into and degrade articular cartilage. As RASF are able to migrate Healthy human cartilage was co-implanted subcutaneously into SCID mice together with RASF. At the contralateral flank, simulating an unaffected joint, cartilage was implanted without cells. To analyze the route of migration of RASF, the cells were injected subcutaneously, intraperitoneally or intravenously before or after implantation of cartilage. In addition, whole RA synovium and normal human cartilage were implanted separately in order to analyze the effects of matrix and other cells on the migratory behavior of RASF. To evaluate potential influences of wound healing, either the primary RASF-containing implant or the contralateral implant without RASF, respectively, was inserted first, followed by implantation of the corresponding other implant after 14 days. After 60 days, implants, organs and blood were removed and analyzed. For the detection of human cells, immunohisto- and -cytochemistry were performed with species-specific antibodies.via the vasculature. With respect to functional aspects, growth factors and adhesion molecules appear to influence significantly the migratory behavior of the synovial fibroblasts.RASF not only invaded and degraded the co-implanted cartilage, they also migrated to and invaded into the contralateral cell free implanted cartilage. Injection of RASF led to a strong destruction of the implanted cartilage, particularly after subcutaneous and intravenous application. Interestingly, implantation of whole synovial tissue also resulted in migration of RASF to the contralateral cartilage in one third of the animals. With regard to the route of migration, few RASF could be detected in spleen, heart and lung, mainly located in vessels, most likely resulting from an active movement to the target cartilage The results support the hypothesis that the clinically characteristic phenomenon of inflammatory spreading from joint to joint is mediated, at least in part, by a transmigration of activated RASF, regulated by growth factors and adhesion molecules.


This study examined the factors that influence condom-use among young never-married males in Nigeria. Such information can help improve the design of a prevention programme for young never-married, especially, males to reduce their vulnerability to sexually transmitted infections (STIs) and HIV/AIDS transmission. Data were derived from the 2003 Nigeria Demographic and Health Survey (NDHS). Analysis of data was restricted to 827 males aged 15-24 years, who had never married or lived together with a woman. Both descriptive and analytical methods were used for assessing the net effects of socioeconomic factors on condom-use. The analysis used logistic regression models for determining the predictors of sexual behaviour and condom-use among young never-married males in Nigeria. About 43% of the study population was sexually experienced, and the use of a condom remained low. One in five reported the use of a condom at sexual debut. Level of education, place of residence in childhood, urban/rural region, religious affiliation, economic status index, and exposure to mass media were associated with sexual experience and use of protective measures. Economic status index and mass-media exposure were associated with the use of a condom by the respondents during their last sex encounter. About two-fifths (43%) of the young unmarried Nigerian men were sexually experienced but the condom-use remained low, thus making this sub-group of Nigerian population highly vulnerable to STIs, including HIV/AIDS. Adolescence is a transition period between childhood and adulthood. This is a time when many young people experience critical life-defining changes, such as their first sexual experience, marriage, pregnancy, and parenthood. Initiation of sexual intercourse has been described as a milestone in the physical and psychological development of men and women in all societies . This epSexual behaviour of adolescents is important not only because of the possible reproductive outcomes but also because risky sexual behaviours, such as unprotected sex and low and inconsistent use of a condom during sexual intercourse, have been associated with HIV infection. Early sexual initiation poses health risks for both young men and women. Most young adults who entered into a sexual relationship for the first time did not use any form of contraception and were ignorant of the consequences of their acts -10 leaviIn Nigeria, sexual activity among adolescents is a concern of public-health priority for government officials, donors, and programme managers because of the serious outcomes usually accompanying teenage unprotected sexual exploitation -18. ThisSensitization and information programmes on the consequences of unprotected sexual intercourse, including HIV/AIDS, have been implemented in Nigeria, along with efforts to promote the use of condoms. These programmes have, however, had limited impact in the translation of knowledge about HIV/AIDS and prevention methods into the adoption of healthy sexual behaviour . EvidencDesigning an effective programme to promote res-ponsible reproductive health behaviour among young adults in Nigeria requires a better understanding of the factors relating to their sexual behaviours. Although scholars have documented factors associa-ted with reproductive health behaviour among Nigerian youths, a few of these have examined sexual behaviour of young never-married males and in particular condom-use at sexual debut. This study examined the predictors of condom-use at sexual debut among young never-married males in Nigeria. Condom-use during the first sexual experience warrants special attention in light of the spread of STIs and the HIV/AIDS pandemic and the increase in unwanted and unplanned pregnancies that may lead to discontinuation of schooling. Overall, this paper focused on understanding the factors affecting condom-use by young never-married males at both sexual initiation and the last sexual act.The study used data from the 2003 NDHS. This nationally-representative sample survey covered 7,864 households located in both urban and rural settings. The area-sampling frame for the survey was based on the enumeration area-maps prepared by the National Population Commission (NPC) for conducting the 1991 census. Selection of sample was made in two stages: first, 365 clusters were selected with equal probability. Second, within each of these 365 clusters, a complete listing was done of all residents in sampled households, from which male and female respondents were interviewed. Details of the research design are available in the 2003 NDHS report . In totaAnalysis focused on four reproductive health behaviours: whether respondents had had sex; whether they had sex in the four weeks before the interview; whether they had used condom at first sexual intercourse and whether condom was used at the last sexual intercourse. Their demographic characteristics were included in the analysis to identify factors for possible intervention and to act as control variables in the analytical models. The characteristics considered were age, the highest level of education completed, place and region of residence, religious affiliation, media exposure, and wealth quintile. Analysis of the first reproductive health behaviour—whether the respondents had had sexual intercourse—was based upon responses provided by all 827 sample respondents. However, analysis of the remaining three reproductive health behaviours was based on 355 respondents who had had sexual intercourse.Both descriptive and analytical analyses were conducted to ascertain the association and net effect of the background characteristics of the respondents on reproductive health behaviours—sexual activity and condom-use—when controls for the selected background characteristics were introduced. The statistical analyses were undertaken in two phases. Bivariate relationships between each of the selected characteristics/predictors and reproductive health behaviours of interest were established. The statistical significance of difference among categories of discrete reproductive health behaviours was tested through Pearson's chi-square statistic.0+B1X1+ … +BkXk, where p is the probabili-ty that a respondent used a condom during sexual debut or the last sexual act; q (or 1-p) is the probability that the respondent did not use a condom at sexual debut or the last sexual act. B0, B1, … Bk are regression coefficients, and X1, X2, … Xk are factors. The exponential of the regression coefficients of the parameter estimated gives the odds ratios in the logistic regression models, which is interpreted as the likelihood of condom used under the given scenarioBackground characteristics for which statistically significant bivariate associations were observed were retained for subsequent multivariate analyses. The four reproductive health behaviours of interest  were binary outcomes. Logistic regression was used for determining the effects of predictor variables on selected reproductive health behaviours. The logistic regression model also offers ease of interpretation through the use of odds ratios. The logistic regression function has the form In (p/q)=BIn total, 827 young never-married males, aged 15-24 years, who were interviewed during the 2003 NDHS, were analyzed in the study. About 70% of the study men had some secondary education. Only 6% of them had post-secondary education, and 8.6% had no formal education. Christians constituted a majority (58%) of the sampled respondents, with three in five young never-married males being Christians. Muslims constituted 41.2%, and less than 1% was adherent to indigenous religions. Another important background characteristic considered in the analysis was the wealth quintile. The wealth quintile constructed from the household facilities was used as a proxy for economic status. The level of wealth quintile ranged from the first to the fifth quintile, corresponding to the least and most well-off res-pectively. The wealth quintile revealed that about one in four young never-married males was from households classified in the fifth quintile.Overall, about 43% of the respondents had ever had sexual intercourse, and the median age at sexual debut was 18 years. About one-fifth of the study population had sexual relations in the month and of those who were sexually experienced, about 47 had sexual relations in the four weeks before interview. Results of analysis revealed that the proportions of the respondents who were sexually experienced and those who had sexual intercourse in the previous four weeks before the interview survey increased with age. For instance, one-fourth of the young never-married male respondents aged 15-19 years and 62% of their older peers aged 20-24 years had ever had sex. The corresponding figures with respect to sexual activity in the past month were about 45% and 47% respectively. Rural residents tended to initiate sexual relations earlier than did urban residents (about a one-year difference) and were slightly more sexually experienced and more sexually active in the last four weeks before the interview. For instance, 45% of the young never-married rural males were sexually experienced compared to 39.6% of their urban counterparts. Childhood place of residence somewhat supported the notion of less-frequent sexual activity among those who had some urban exposure. However, the age at sexual debut was generally higher among those with higher level of education compared to those with lower level of education. This finding indicates that young never-married males with no formal education started sexual activity two years earlier than those with tertiary education.Religion is believed to have a profound impact on individual behaviour and views ,28. EvenIn the logistic regression model , young nWith respect to correlates of current sexual activity in the last four weeks preceding the survey, loresidence, religious affiliation, and frequency of watching television were significantly associated with whether the young never-married males engaged in premarital sex in the last four weeks before the survey. Those who resided in the southeast region were almost four times less likely to engage in sex in the previous four weeks compared to their counterparts from the north-central region.About two-fifth (43%) of the young never-married males in Nigeria were sexually experienced, the level of condom-use among them was low—an indication of a high level of their vulnerability to STIs, including HIV. Seventeen percent of the young never-married males who were sexually experienced used condom at the time of their first sexual act . Table 4The findings in About two-fifths (38%) of sexually-active young never-married males used a condom at the time of their last intercourse. Despite a high level of sexual activity among the young never-married males, the level of condom-use among them was low, an indication of high level of their vulnerability to STIs, including HIV. The results in This study found a high level of premarital sexual activity among the young never-married males. Age at initiation of sex remained low and current sexual activity high, although the personal and sensitive nature of questions on sexual activity make reports of age and level prone to deliberate misinformation. The results also suggest that a large proportion of young never-married males engage themselves in sexual intercourse without a condom, thus increasing their vulnerability to STIs and unwanted pregnancies. For instance, the level of condom-use at sexual debut was 17%, and 38% used a condom during their last sexual act. The low level of condom-use at sexual debut is comparable with earlier analysis in Nigeria  and otheThe results of the present study revealed that the young never-married males who were at the greatest risk of adverse reproductive health behaviours appeared to be from families of low economic status, those who resided in rural areas, and those who lived in the countryside during their childhood. This could be explained by the fact that the majority of the young never-married males from these backgrounds might have been denied sex education, thus making them ignorant of what they needed to do for protection. In addition, the parents, the family, and the community members expect that social and traditional norms should be adhered to strictly; however, the influence of sociocultural norms are being eroded as a result of poverty and education, thereby often exposing them to risky behaviour. The social and traditional norms which prohibited sexual intercourse before marriage are being eroded due to increased age at first marriage being observed  and expoThe regional patterns of sexual behaviour  found in this study suggest that ethnicity may be an important factor to be considered when studying adolescents or young people's sexuality and sexual behaviour. However, this influence of cultural norms may be changing due to globalization and education, especially in cities where people are more likely to abandon traditions because of the heterogeneity of populations. Still for many Nigerians, ethnic affiliation, which is usually a regional element, means shared language and norms governing behaviour and sexuality issues. The results of this study support the view that condom-use and age at sexual debut in Nigeria are a function of varied sociocultural factors, including religion, level of exposure to formal education, and urban-rural residence among others.Apart from the regional differences in sexual behaviour observed in the study, several results showedthe association between the characteristics of youngnever-married males and condom-use. Comparedto rural dwellers, those residing within urban environments were more sexually experienced and more likely to use a condom at the first coitus. Thehigh level of sexual activity among the urban young never-married males can be seen in the context of a permissive environment which favours theattraction and interaction of youths of opposite sex and which, therefore, exposes them to sexual contact. The same factor, however, serves as a protective mechanism by encouraging the use of a condom due to high level of awareness on the intrinsic worth of condom-use. The result of the study also indicates that growing older is associated with sexuality and condom-use among young never-married males in Nigeria. The finding of the study supports the view that sexual activity and condom-use are functions of household socioeconomic status .The results of the study shed further light with regard to the challenges facing programmes aimed at improving the reproductive health situation of adolescents and young never-married males in Nigeria and opportunities for intervention. One major challenge is the sizeable number and diverse nature of factors that appeared to influence behaviour of young never-married males. Some of these were particular characteristics of the environment in which they are reared. Therefore, a single, easy-to-implement intervention is unlikely to provide a solution to the high rate of sexual activity and its consequences of teenage pregnancy and vulnerability to STI and HIV/AIDS transmission in Nigeria. This is consistent with the findings of a previous study which revealed that, when in a given setting and a multitude of correlates exists, each having a small impact on sexual behaviour rather than a few correlates, each having a large impact, a single ‘magic bullet’ is unlikely to be found to change sexual behaviour of adolescents significantly .The results of the study have important policy implications. Since the factors associated with sexual behaviour and condom-use among never-married young Nigerian males vary according to place of residence, region of residence, exposure to mass media, and wealth quintile, programmes may need to position intervention differently for different target populations. The study established that there is a high level of unprotected premarital sex, thus making the population under study vulnerable to HIV infection. In addition, an unwanted pregnancy could lead to termination of education; as a result, young women and men could face a bleak economic and social future. Therefore, behaviour-change communication should be streng-thened with extensive education on sexual abstinence and safe sexual behaviour through culturally-appropriate messages as is currently undertaken by various non-governmental organizations in the country. In particular, more efforts should be made to reach young never-married males in the countryside, who typically had earlier sexual debut and also tended to be more sexually active, with adequate information on behaviour change, prevention of unwanted pregnancies, and protection from STIs, including HIV/AIDS.The authors acknowledge the helpful comments of Dr. Bamikale Feyisetan of the Academy of Education Development, USA, in the preparation of this article. In addition, the authors thank the Marco International and National Population Commission, Nigeria, for making the data of the Nigeria Demographic and Health Survey available for use.