Receptor tyrosine kinase-like orphan receptor 1:A novel antitumor target in gastrointestinal cancers

Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.

Neurologic orphan diseases:Emerging innovations and role for genetic treatments

Orphan diseases are rare diseases that affect less than 200000 individuals within the United States.Most orphan diseases are of neurologic and genetic origin.With the current advances in technology,more funding has been devoted to developing therapeutic agents for patients with these conditions.In our review,we highlight emerging options for patients with neurologic orphan diseases,specifically including diseases resulting in muscular deterioration,epilepsy,seizures,neurodegenerative movement disorders,inhibited cognitive development,neuron deterioration,and tumors.After extensive literature review,gene therapy offers a promising route for the treatment of neurologic orphan diseases.The use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several diseases.Additionally,the use of adeno-associated viral vectors has shown improvement in survival,motor function,and developmental milestones,while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia patients.Antisense oligonucleotides have also been used in some neurologic orphan diseases with positive outcomes.Mammalian target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth,proliferation,and angiogenesis.Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.

World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients

According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.

Analysis Toward Charles Dickens “Hope and Despair” in “Trilogy of Orphans”

In the middle of the 19th century, with a series of excellent novels the great British critical realist writers Charles Dickens created us a vivid world of"hope and despair". Of all his voluminous works, the famous"trilogy of orphans"is all representatives of"hope and de spair. which not only greatly influenced many contemporary writers, but also used for reference by the budding young writers.

Candidate members of the Pal 5, GD-1, Cetus Polar and Orphan tidal stellar halo streams from SDSS DR9, LAMOST DR3 and APOGEE catalogs

We present candidate members of the Pal 5, GD-1, Cetus Polar and Orphan tidal stellar streams found in LAMOST DR3, SDSS DR9 and APOGEE catalogs. In LAMOST DR3, we find 20, 4 and 24 high confidence candidates of tidal streams GD-1, Cetus Polar and Orphan respectively. We also list 59, 118 and 10 high confidence candidates of tidal streams Cetus Polar, Orphan and Pal 5, respectively from the SDSS DR9 spectroscopic catalog. Furthermore, we find seven high confidence candidates of the Pal 5 tidal stream in the APOGEE data. Compared with SDSS, the new candidates from LAMOST DR3 are brighter, so that together, more of the color-magnitude diagram, including the giant branch, can be explored. Analysis of the SDSS data shows that there are three metallicity peaks associated with the Orphan stream which also exhibit some spatial separation. The LAMOST data confirm multiple metallicities in this stream. The metallicity, given by the higher resolution APOGEE instrument, of the Pal 5 tidal stream is [Fe/H] ,- -1.2, higher than that given earlier by SDSS spectra. Many previously unidentified stream members are tabulated here for the first time, along with existing members, allowing future researchers to further constrain the orbits of these objects as they move within the Galaxy＇s dark matter potential.

Functional analysis of the orphan genes Tssor-3 and Tssor-4 in male Plutella xylostella

Orphan genes are genes with no sequence homologues in other species. Here, we identified two orphan genes, namely, Tssor-3 and Tssor-4, in Plutella xylostella. Both genes contained a signal peptide sequence, suggesting their functions as secreted proteins. Expression pattern analysis based on real-time quantitative PCR(qPCR) showed that both orphan genes were specifically expressed in all male gonads except the testes. The expression of both the orphan genes peaked at the male adult stage. Immunofluorescence assays suggested that the two proteins were seminal proteins, indicating their potential roles in male reproductive regulation. To further explain their functions, we knocked down the expression of these two genes by RNA interference(RNAi). The results showed that the expression of Tssor-3 and Tssor-4 was significantly downregulated at 24 h after injection compared to that of the controls. Biological assays showed that the number of laid eggs and the hatching rate of offspring eggs were significantly reduced when the expression of Tssor-3 and Tssor-4 was reduced, suggesting that the two orphan genes played a role in male fertility in P. xylostella. Our results provide evidence that orphan genes are involved in male reproductive regulation, which is important for male fitness during evolution.

Lay vs. Professional Perspectives: The Sexual and Reproductive Health of Orphans and Vulnerable Children in Uganda

Background/Introduction: Orphans and vulnerable children (OVC) in sub-Saharan Africa have been the focus of much popular and academic writing and the growing body of evidence cannot be overlooked. Existing research focuses on projections of OVC numbers, interventions, outcomes and descriptions of care arrangements. A lot of information exists on their poor sexual and reproductive health (SRH) status—most of it quantitative. The purpose of this paper is to present the voice and perceptions of OVC in regards to their SRH. Methods: This was a mixed-methods qualitative study drawing from phenomenology and it used purposive sampling to recruit 129 participants. Results: OVC perceptions and priorities do not always intersect with those of professionals and this has implications for existing and planned interventions. For example some OVC think favorably about early marriages while others have mechanisms of self-protection again SRH harm although this is not usually acknowledged. Conclusions: OVC demonstrate agency;therefore positioning them at the heart of service planning and delivery is an effective strategy in increasing the uptake and impact of interventions seeking to address their sexual and reproductive health needs.

Living status and support system of children orphaned by AIDS in central China—Description and policy recommendations

This study aimed to research the living status and support system of children orphaned by AIDS in rural Henan Province. The approach of face-to-face questionnaires research was used to assess 501 children’s current situation while in-depth interview was conducted for the support system research. The age range of the children orphaned by AIDS was 2 - 15 years old and the mean age was 11.10 years. Most children among 2 - 6 years had communication skills with temper control and psychological problems. Children of 7 - 15 years old had the ability to take care of themselves and family members but could not do self-regulation. The support system for children orphaned by AIDS included social support, policies support, education support, and health care support but improvement are needed in the future. Support system can be improved through much more feasible and concrete policies and strategies to guarantee these children’s basic needs and comprehensive development.

Nutritional Intervention at a Girl’s Orphanage in Sri Lanka Decreased Stunting after One Year

Background: Both the civil war in 1998 and the tsunami in 2004 in Sri Lanka resulted in a large number of orphans. Objective: To examine the effect of nutritional intervention on one-year period of stunting and/or emaciated status. Methods: Study setting: Twenty-eight girls aged 5 - 19 years old were in the care of Grace Girls’ Home, an orphanage for girls located in the port town of Trincomalee, Sri Lanka, at the time of the survey. Nineteen of them had two available anthropometric measurements recorded over one year of follow-up. Anthropometric measurements were obtained prior to the intervention of nutritional mentoring to the local caregivers, and one year after intervention. Height-for-age, weight-for-age, and BMI-for-age z-scores were calculated using SMART methodology. Nutritional consultancy recommended an additional 15 - 20 grams of high quality protein per day, which was given to the girls. The kitchen team was encouraged to regularly prepare a variety of pulse-based dishes, using local foods and recipes. The local palm oil, rich in saturated fatty acids, was replaced with sunflower oil, rich in polyunsaturated fatty acids. Results: Stunting was decreased from Height to age Z-score (−1.19 ± 0.94) to (−0.90 ± 1.06) (P = 0.016), and BMI Z-score from (−0.80 ± 0.79) to (−0.50 ± 0.74) (P = 0.004). Conclusions: A single nutritional education intervention, culturally adapted and implemented by the local caregivers, can decrease stunting in orphans within one year.

Care and Support Programmes for Orphans and Vulnerable Children: Achievements and Implications of HIV/AIDS Funded Project in Osun State, Nigeria

Orphans and Vulnerable Children (OVC) and their families face many challenges but there are opportunities to provide care and support programmes for them in their communities. This paper presents the achievements and implications of HIV Programme Development Project (HPDP) funded by World Bank on care and support services for OVC in Osun State, Nigeria. Eight Civil Society Organisations (CSOs) were engaged by Osun State Agency for the Control of AIDS (OSACA) as part of HPDP to provide care and support services for OVC between year 2013 and 2015. Using reporting tools, data collected by the CSOs were entered into District Health Information System 2 (DHIS2) platform and analysed using Microsoft Excel. In addition, Key Informant Interviews (KII) were conducted among the selected CSOs, OVC and the caregivers who were beneficiaries of HPDP in Osun State, Nigeria. A total of 12,353 OVC were reached and about half of them were female. There was an increase in the trends of number of OVC seen and the support services provided from the year 2013 to 2015. Of the 12,353 OVC that benefitted from this programme, 1905 (15.4%) received health care services, 5383 (43.6%) received nutritional services, 5317 (43.0%) received educational services and 9861 (79.8%) were provided with psychosocial support services. About 503 (4.1%) of the OVC received economic strengthening services while 270 (2.2%) of household heads were provided with economic support. However, 3 OVC were lost to follow-up, 14 OVC voluntarily withdrew from the project and 6 OVC died. The FGD and KII revealed that the project was very impactful in transforming the lives of the OVC. Programmes for children orphaned and made vulnerable by HIV/AIDS will contribute to the achievement of HIV/ AIDS prevention and control efforts. The HIV/AIDS free generation can be built by responding to the physical, social and mental needs of these children and their families in their communities. There is a need to scale-up this programme.

A Public Health Model and Framework to Mitigate the Impact of Orphans and Vulnerable Children Due to HIV/AIDS in Cameroon

UNICEF, UNAIDS and USAID developed a global strategic framework to guide responses to care and protect orphans and other vulnerable children in the context of HIV/AIDS. In the developing world, about 132 million people have lost one or both parents due to the AIDS pandemic and 25 million children have been orphaned by HIV/AIDS in 2010. The HIV prevalence in Cameroon is estimated at 5.1%. As of 2010, there were 304,000 deaths due to AIDS in Cameroon. Out of 1,200,000 orphans and vulnerable children in Cameroon in 2010, 300,000 were AIDS orphans. The HIV/AIDS burden impacts child survival, growth and development in the traditional African setting. With so many orphans in the population, along with many vulnerable children, strategies must be developed to respond more effectively to their critical needs. This study provides a model for OVC care and support in Cameroon. The model was developed out of extensive work using a participatory approach involving traditional, administrative and health stakeholders on OVC in Yaounde I and Yaounde VI Councils, Nanga Eboko Health District, Isangelle, Ekondo Titi, and Bafaka-Balue communities in Cameroon. Consultancy services with PLAN Cameroon, the Pan African Institute for Development-West Africa coupled with facilitation of many training workshops on OVC with Save the orphans Foundation, the Ministry of Social Affairs, and the Ministry of Public Health and working with the National AIDS Control Committee. The essential components of a holistic framework for the care of OVC have been identified. A public health model for the care of OVC and a mechanism for their identification and a referral system for testing OVC for HIV are proposed. Through this model, a mechanism for the effective holistic care of OVC and collaboration is enhanced.

Employing Orphan Nodes to Avoid Energy Holes in Wireless Sensor Networks

When energy consumption by wireless sensor nodes gets off balance, partitions in the network appear because several of the nodes stop functioning. The respective network’s lifetime also diminishes. This problem is commonly known as the “hot spot” or “energy hole” phenomenon. To resolve this issue, a Multi-Hop Decentralized Cluster-Based Routing (MDCR) protocol is proposed. This algorithm uses orphan nodes as intermediate nodes to form inter-cluster multi-hop routing and balance the energy consumption among sensor nodes. Simulation experiments have shown that MDCR is significantly better at prolonging network lifetime compared to the Adaptive Decentralized Re-Clustering Protocol.

The Legal Protection of Children Orphaned by HIV/AIDS in Nigeria: An Appraisal

The Human Immunodeficiency Virus and the resultant disease—Acquired Immune Deficiency Syndrome are global epidemics in recent times. Although the effects of the epidemic have been curtailed somewhat in the developed world, it is not so in developing countries. As such it affects not only the infected but those directly dependent on them. Some of the affected people have been identified as children, who turn out to be unprepared for and defenceless against the imminent hardship prevalent as a consequence of the disease. The effects of the epidemic are felt more in the developing world than in developed countries and this is because the attitude of the developed world to the epidemic is positive, enhanced by awareness of the disease;whereas in the developing countries, a lot of myths are attached to it, affecting the requisite attitude needed to combat the epidemic and its effects. This paper seeks to examine the effects of this epidemic on children in Nigeria, comparing the effects on children in other African countries. The paper also looks at structures in place to cater for these children, and then seeks to proffer improved means of protecting their rights.

Risky Sexual Behavior and Its Determinants among Orphan and Vulnerable Children in Addis Ababa, Ethiopia

Back Ground: Risky sexual behavior among orphans and vulnerable children and its associated physical, psychological and social consequences is becoming a major public health concern globally. Objectives: To assess the prevalence of risky sexual behavior and its determinants among orphan and vulnerable children in Addis Ababa. Methodology: A community based cross sectional study was conducted on three support and care giving organizations for orphans and vulnerable children in Addis Ababa, Ethiopia from March to June 2014. A total of 422 orphan and vulnerable children were selected using systematic sampling. Data were collected using pre tested self-administered questionnaire. Logistic regression was used to analyze the data. Result: A total of 407 (96.4%) respondents participated in this study. Among them 112 (27.5%) had sexual intercourse in their life time, of these 50 (44.6%) started sex before the age of 15, 94 (83.9%) had forced sex, 84 (75.0%) had multiple sexual partners, only 16 (14.3%) used condom the first time they had sex and 96 (85.7%) participated in transactional sex. Females were about 3.25 (2.67 - 7.3) times more likely to engage in risky sexual behavior than male respondents, double orphans had 4.32 (2.45 - 9.54) odds of risky sexual behavior compared to their counterparts. Those respondents who had knowledge of HIV transmission and prevention were less likely to be involved in risky sexual behavior 0.58 (0.41 - 0.93). Conclusion: Orphan and vulnerable children are at a higher likelihood of risky sexual behavior. Intervention targeted at multilevel such as orphan survival training, assertive communication skills, sexuality education and education about HIV risk perception, physical, psychological and human right protection, social support, and economic access for basic needs need to be given consideration.

Orphan and Rare Disease Products -The Payer Perspective

The paper is to look at the affordability of orphan medications across the globe and whether payer attitudes to high-price medications are changing in the face of rising healthcare expenditure and tighter budgets. We conducted an online semi-quantitative survey of 10 European markets, the United States and Japan （Q1-Q2 2014） to understand how payers＇ views and attitudes are changing in response to new treatments coming to market for rare and ultra-rare conditions. The payers selected for the survey hold or have held senior positions within their respective market institutions. The United States and Japan were included in the study to provide international context to the European results. Responses were anonymised in accordance with good market research principles. The research shows that 75% of respondents surveyed believe that the current approach to orphan drug pricing is unsustainable in the future and 92% predict a tougher approach from payers going forward. 75% of payers do not believe that patent expiry alone will free up the necessary space for innovative orphan and ultra-orphan products. 83% of the payers surveyed believed that less than half of all orphan and ultra-orphan drugs coming to market are supported by an adequate evidence base for reimbursement. The environment for orphan medicines across the globe is changing; and as the financial performance of countries begins to diverge, so do attitudes towards the funding of orphan medicines. The increasing number of rare diseases, and treatments available, is forcing payers to view orphan drugs in a new light and they are becoming increasingly sceptical about the prices charged in relation to the clinical benefit offered. As rare disease spending becomes a higher proportion of pharmaceutical spending, payers will need to take action to curb this trend.

The Rehabilitation of the Orphans in the Deep South of Thailand

The purposes of the research aim to： （1） investigate the rehabilitation of the orphans affected by the violence in the Deep South of Thailand; and （2） provide the guideline for the government and institutions to find ways to rehabilitate the orphans affected by the violence in the Deep South of Thailand. The number of the orphans is drastically increasing because of the violence crisis for a long time since 2004. The government has the policy to rehabilitate the orphans affected by the violence and takes the scholarships for relief their mind related injury Surveillance. The orphans trust the civil society more than the public government. Some opinions suggest the education, the activities, i.e., sports, music to empower the orphans, and the roles of the family and family members are the most important to take care and rehabilitate the orphans by using the religion for conducting ＂the social well-being＂.

An orphaned Section of the Great Wall

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Chinese Company Doubles as “Mother” of Orphans

The story goes back to the end of 2007, when Yang Min, Party secretary and deputy chief manager of theNantong Times Clothing Co., Ltd. in Rugao, Jiangsu Province, heard what had happened to an orphan in the city.

Management of Orphan Drug Reimbursement Abroad and Its Enlightenment to China

Objective To analyze relevant policies and measures on the management of orphan drug reimbursement in foreign countries to provide a reference for future reimbursement management in China.Methods According to the percentage of health care expenditure in GDP,the completeness of rare disease policies,and the total population,Russia,Australia,and India were selected as the reference.Based on the existing literature,the main content and characteristics of the reimbursement of rare disease drugs were analyzed.Results and Conclusion Russia manages rare diseases in the form of lists.Special rare diseases are reimbursed by federal or regional finances,and ordinary rare diseases are reimbursed by statutory medical insurance funds.Orphan drugs in Australia are included in the pharmaceutical benefits scheme(PBS)and the lifesaving drugs program(LSDP),LSDP provides fully reimbursed drugs for eligible rare disease patients.India’s proposal takes health system sustainability into consideration.China should carry out epidemiological research to legally determine the rare diseases,establish reasonable reimbursement standards,and improve the multi-level reimbursement system.

Grow Together under the Sunshine——The 4th Summer Camp for AIDS Orphaned Children

The 4th summer camp for AIDS-orphaned children was held in Beijing from August 2-8, 2007. Co-sponsored by the China Youth Concern Commission and China Foundation for the Prevention and Control of STDs （sexually transmitted disease） and AIDS, the event was attended by 80 AIDS-orphaned children aged 8- 16 from 18 counties and cities of 8 provinces of Shanxi, Yunnan, Henan, Jilin, Liaoning, Guizhou, Sichuan and Anhui.