Neonatal hearing screening (NHS) has been routinely offered as a vital component of early childhood care in developed countries, whereas such a screening program is still at the pilot or preliminary stage as regards its nationwide implementation in developing countries. To provide significant evidence for health policy making in China, this study aims to determine the cost-effectiveness of NHS program implementation in case of eight provinces of China.A cost-effectiveness model was conducted and all neonates annually born from 2007 to 2009 in eight provinces of China were simulated in this model. The model parameters were estimated from the established databases in the general hospitals or maternal and child health hospitals of these eight provinces, supplemented from the published literature. The model estimated changes in program implementation costs, disability-adjusted life years (DALYs), average cost-effectiveness ratio (ACER), and incremental cost-effectiveness ratio (ICER) for universal screening compared to targeted screening in eight provinces.A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios using a probabilistic modeling technique. Targeted strategy trended to be cost-effective in Guangxi, Jiangxi, Henan, Guangdong, Zhejiang, Hebei, Shandong, and Beijing from the level of 9%, 9%, 8%, 4%, 3%, 7%, 5%, and 2%, respectively; while universal strategy trended to be cost-effective in those provinces from the level of 70%, 70%, 48%, 10%, 8%, 28%, 15%, 4%, respectively. This study showed although there was a huge disparity in the implementation of the NHS program in the surveyed provinces, both universal strategy and targeted strategy showed cost-effectiveness in those relatively developed provinces, while neither of the screening strategy showed cost-effectiveness in those relatively developing provinces. This study also showed that both strategies especially universal strategy achieve a good economic effect in the long term costs.Universal screening might be considered as the prioritized implementation goal especially in those relatively developed provinces of China as it provides the best health and economic effects, while targeted screening might be temporarily more realistic than universal screening in those relatively developing provinces of China. As adequate auditory stimulation in early childhood is fundamental for optimal speech and language development as well as for the acquisition of literacy skills, early hearing detection and interventions for deaf children are essential ,2. A faiNeonatal hearing screening (NHS) program has made a rapid development in recent years. The benefit of NHS is that it allows most PCEHI to be detected early enough for optimal intervention ,12. NHS Cost-effectiveness analysis (CEA) has been used as a tool to prioritize scarce health resources, which allows the comparison of various intervention options ,15. AlthIn China, the largest developing country in the world, the Ministry of Health has recently decided to address the issue of non-fatal congenital diseases in neonatal health care which have until now been neglected but have a considerable impact on the individual, family and society. There is now a political commitment to scale-up a hospital-based neonatal hearing screening program, which will include expanded screening, diagnosis and intervention services . A key pIn the present study, we modeled the cost-effectiveness of two screening programs: universal screening which covers all live births, and targeted screening which targets those with one or more risk factors Figure . UniversA natural history model of all infants with and without hearing impairments was developed to characterize the process of screening, diagnosis and interventions through all possible stages. All neonates annually born in eight provinces  of China from 2007 to 2009 were simulated , diagnosis rate which shows those diagnosed before 6 months among those referred after the screening, and intervention rate which shows infants fitted with hearing aids or cochlear implants and that have started the rehabilitation course before 12 months of age among those with the disorder as detected by the diagnosis process , recurrent costs such as the salaries of the personnel, materials and supplies, utilities, equipment maintenance, database management, training and transport, and patient-level costs which were composed of the registration fee, screening tests, diagnosis tests, drugs, treatment with a hearing aid, treatment with a cochlear implant, rehabilitation courses, and transportation charges for diagnostic procedures and treatments. The capital investments of office buildings, furniture and equipment were annualized by depreciation, for which the life spans were standardized by Ministry of Finance of the People's Republic of China and Ministry of Health of the People's Republic of China [We followed the guideline developed by the World Health Organization (WHO)  to estimof China  Table 2 of China .Apart from the costs of program implementation for estimates of cost-effectiveness, it is reasonable to assume (and thus estimate) that money would be saved if early detection and intervention was given. Early detection and intervention may bring expenditure on special education and rehabilitation reduction, social and medical services support decrease and incomes increase. However, there was no report on the long-term costs of the disorder from the published literature in China. In our model, we preliminarily attempted to estimate the potential long-term costs saving from the use of the NHS program, including medical services, special education and rehabilitation. It was assumed that improved language outcomes would result in a 10% decrease in special education costs and a 75% decrease in vocational rehabilitation costs ,41. It wData collection in the field included two components: costs related to the screening program which were acquired from general hospitals and maternal and child health hospitals providing screening and diagnosis services, and rehabilitation facilities, and transition probability parameters including the coverage of screening program, the diagnosis rate and intervention rate which were calculated based on data from the database established at the provincial level. A multiple of three parameters shows the proportion of infants with PCEHI potentially benefiting from the screening program among the targeted population , in this study, calculated as the proportion of the benefit population .After permission to use the database by the district health agencies, the data of the province were acquired. For the costs estimate, all facilities providing screening, diagnosis, and rehabilitation services were visited in selected districts and the annual financial report was analyzed by an expert in hospital accounting.In this study, population health is expressed as the number of Disability-Adjusted Life Years (DALYs) averted as a result of the screening program. DALYs lost due to PCEHI were calculated as the sum of Years Lost due to Disability (YLDs), as it is a non-fatal disorder, and the time period is life-long. Disability weights for adult-onset hearing impairment were adopted in the estimation, 0.216 for untreated disorders and 0.168 for treated disorders, respectively . This waThe cost-effectiveness of a given intervention is typically expressed as costs per unit of effectiveness, with costs measured in monetary terms and effectiveness measured in health metrics terms. In this study, the average cost-effectiveness ratio (ACER) is calculated for each screening strategy by determining the cost for the program's implementation (except long-term costs saving) and total health effects in terms of DALYs averted. Incremental cost-effectiveness ratio (ICER) shows the absolute value of resources necessary to move to the next option. We calculated ICER for different screening strategies by dividing the incremental costs by the incremental health effects, in order to determine the priority of purchasing these services at different budgetary levels.A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios, using a probabilistic modeling technique, known as Monte Carlo simulation. The simulation associating the estimates of costs and health effects as described above with each of the transition probability parameters was performed on one parameter at a time allowing for the input of extreme values while keeping the other parameters fixed at the their baseline level. The model was evaluated on 1,000 trials. It showed that any variation in the input parameter might result in a change of preference of strategies compared to the baseline result.Demographic and socioeconomic information and the indicators of the program implementation including coverage rate, diagnosis rate and intervention rate in the six provinces were presented in Table Table Multivariate sensitivity analyses were performed for transition probability parameters to determine the robustness of the model. The results suggested the variables whose range of uncertainty had a great impact on the cost-effectiveness of the screening strategies were the program coverage, diagnosis rate, and intervention rate. Figure Costs would be saved if early detection and intervention was given. In our model, universal strategy and targeted strategy led to 214,024,820 and 104,872,740 Int$ of long-term costs saving in total which are approximately equivalent to 0.14% and 0.07% of the annual health expenditure .At the baseline, both strategies achieve cost savings which were greater than implementation costs. When the proportion of benefit population expanded, the effect of these screening strategies on the long-term costs saving become more and more significant, especially those of universal strategies, exceeding the total costs of the screening program implementation, suggesting a good economic effect in the long term Figure .WHO has recommended the implementation of NHS program in member states, particularly in developing countries, based on the experiences and contributions of leading experts from various world regions and across relevant disciplines . This stCan the national plan help the NHS program achieve its goal with good cost-effectiveness, health and long-term economic effects, at both the national and the regional level? The goal of the NHS program in China is to establish a nationwide hospital-based universal program and to continuously expand diagnosis and intervention services . The ratThe study also attempted to estimate the long-term economic effect of the NHS program in China. As the available data and evidence is limited and this is a very preliminary approach, only costs saving in rehabilitation and special education up to 15 years of age (at which children finish their compulsory education) were counted, potentially leading to an underestimate of the economic effect. Even so, the results showed that at the baseline, the costs saved already exceeded the implementation costs in the targeted strategies; as the proportion of the benefit population expends, the economic effect would be more and more significant, especially in relation to universal strategies. Such results strongly support the implementation of the NHS program and suggest potentially greater benefits of adopting universal strategies in China.Our study was restricted by the limited availability of data and evidence. First, globally, there was no strong evidence based on randomized controlled trials for the effectiveness of NHS on deaf infants' language development, and consequently, no evidence as regards the evaluation of their psychological and educational-related outcomes. The impact of early intervention on long-term cost saving remains unknown. Moreover, in China, there has been no previous nationwide population-based study to survey the epidemiological status of PCEHI. Data on the prevalence used in this study were therefore derived from a crude estimation based on the number of the hearing disabled population and a few regional surveys. All that needs to be researched in future. Last, due to the unavailability of child-onset disability weights for hearing loss, we attempted to use adult-onset disability weights instead into the economic evaluation. It may underestimate the health effects of NHS as early detection and intervention leads to much more benefits on children's language development.In conclusion, universal strategy can be considered as the ultimate implementation goal as it provides the best health and economic effects. A universal strategy is feasible in provinces where screening, diagnosis and intervention services are good enough to benefit sufficient proportion of the deaf children. In the other regions, a targeted strategy is temporarily more realistic than a universal strategy; however, related services still need to be scaled up to cover the targeted population as much as possible. The reference data from this study thus are expected to be of particular benefit in terms of the 'rolling out' of the national plan.PCEHI: Permanent congenital and early-onset hearing impairment; NHS: Neonatal hearing screening; CEA: Cost-effectiveness analysis; DALYs: Disability-Adjusted Life Years; YLDs: Years Lost due to Disability; ACER: Average cost-effectiveness ratio; ICER: Incremental cost-effectiveness ratio.The authors declare that they have no competing interests.WT, LZX and DMH designed the study. LHH, LZ, RYGT, FHQ, LS, YT, QLK, FM, XFZ, MZ, RLY, LT, HHL, YQG, SNX, XYY, XDL, BEQ and XHC collected data for the study. LHH, LZ, RYGT and FHQ analyzed the data and contributed to the writing of the paper.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/97/prepub


Understanding environmental factors that influence food-related behaviors among this population will be important to improving the well-being of colonia households. This article focuses on cultural repertoires that enable food choice and the everyday uses of technology in food-related practice by Mexican-immigrant women in colonia households under conditions of material hardship. Findings are presented within a conceptual framework informed by concepts drawn from sociological accounts of technology, food choice, culture, and material hardship.Mexican-origin women in the U.S. living in promotora-researchers  and public-health professionals trained as participant observers. They conducted observations on three separate occasions  within eight family residences located in colonias near the towns of Alton and San Carlos, Texas. English observations were coded inductively and early observations stressed the importance of technology and material hardship in food-related behavior. These observations were further explored and coded using the qualitative data package Atlas.ti.Field notes were provided by teams of colonia residents. Food-related practices were constrained by climate, animal and insect pests, women’s gender roles, limitations in neighborhood and household infrastructure, and economic and material resources.Technology included kitchen implements used in standard and adapted configurations and household infrastructure. Residents employed tools across a range of food-related activities identified as forms of food acquisition, storage, preparation, serving, feeding and eating, cleaning, and waste processing. Material hardships included the quality, quantity, acceptability, and uncertainty dimensions of food insecurity, and insufficient consumption of housing, clothing and medical care. Cultural repertoires for coping with material hardship included reliance on inexpensive staple foods and dishes, and conventional and innovative technological practices. These repertoires expressed the creative agency of women This research points to the importance of socioeconomic and structural factors such as gender roles, economic poverty and material hardship as constraints on food choice and food-related behavior. In turn, it emphasizes the innovative practices employed by women residents of colonias to prepare meals under these constraints. It was discovered that food-related behaviors were shaped by their limited material resources: the built environment, including the material infrastructure of homes and neighborhoods; the tools used in daily food-related activities; and their sometimes limited food supplies. In turn, women residents creatively employed a repertoire of inexpensive staple foods and dishes; inexpensive, common, and mostly unspecialized household items; and home infrastructure to accommodate the socioeconomic, biological and physical constraints of their environment, especially the material hardships endemic to life in the colonias.The hy foods , high lehy foods , low heahy foods , and grehy foods  and obeshy foods . With thworkers)  were askcolonias along the Texas border with Mexico is almost entirely Hispanic, and the household income of approximately 80% of the residents are at or below the poverty level [Colonias are unincorporated functionally-rural communities built on subdivided land. Colonias serve as an archetypal example of new-destination Mexican immigrant communities [Colonias typically consist of low-income housing, non-existent to inadequate infrastructure, and self-build dwellings [colonias, there were 1,092 colonias with a population of 249,675 residents with full or partial services and 442 colonias with a population of 62,675 residents without services [colonias in this study were located in Hidalgo County which is home to more than 70% of Texas border colonias, suffers from persistent poverty and is one of the ten poorest counties in the United States [The population of ty level . Coloniamunities -10. Colowellings . In 2006services . The cold States . In 2010d States .Colonia homes have been described as self-build [lf-build  housing.colonias is their limited access to basic infrastructure. The absence or limited presence of potable water, drainage, sewers, gas, and electricity informs this understanding of the hardships experienced by colonia households [colonia to function like a standard U.S. incorporated neighborhood or subdivision is limited due to endemic neighborhood poverty and the extra-jurisdictional location of many colonias[colonias depends on whether they are connected directly to services [A common characteristic of useholds ,14. The  colonias. Likewisservices .colonia households are described. These include the household setting, which is situated at the intersection of the household with biological, physical and socioeconomic contexts [colonia context.Food choice has been described by Sobal and colleagues as operating within a nested system of contexts . In Figucontexts . The houFood choice entails a material context which includes food-related technology. Research on household technology emphasizes the importance of examining the effect of that item’s use as it interacts with other elements of the home food environment, and with intervening human and non-human forces from outside the home -23.The socioeconomic contexts that frame the use of food-related household technology are rooted in an account of culture that examines the interplay between human agency and the structural constraints that arise from membership in heterogeneous social group formations such as race and ethnicity, gender and socioeconomic class -29. Contcolonia setting, the employment of cultural repertoires such as food-related technological practices are largely constrained rather than enabled by social structure. The term material hardship employed by scholars of poverty to describe the condition of households that fall below minimum standards for the consumption of basic needs is used to capture these constraints on agency [In this paper it is argued that food choices are acts of agency enabled by cultural repertoires. The selection of particular foods or ingredients, the preparation of particular dishes, or the use of food-related technology, are in part the product of the constraints and opportunities of an individual’s social position as defined within the constraints of social structure. Within the n agency ,35.colonia households. These cultural repertoires were in turn evidenced in their selection of foods and dishes, and in their food-related technological practices.In this study, the agents of food choice express cultural repertoires to cope with conditions of material hardship. The forms of material hardship provide a structural context that frames the cultural repertoires used by Mexican-origin women residents of these promotora-researcher and a researcher with a graduate degree in public health. Each team conducted two four-hour weekday visits and one eight-hour weekend visit to four households for a total of eight households between the two teams. The promotoras in this study were previously involved in delivering services to these colonias. They recruited households based on prior familiarity, and their expectation the participants would be likely to complete the study. This research was approved by the Texas A&M University Institutional Review Board and study participants signed an informed consent form.In this participant-observation project, households were observed by two bilingual teams of trained researchers, consisting of a local colonia residents. Participant observers were instructed to note the material aspects of the home food environment including where food was obtained; what foods were preferred by families; how food affected family interactions; what happened during food preparation (including where food was prepared and by whom) and the main techniques of preparation; and to describe characteristics of the specific family. In this study, participant observation allowed access to tacit technological practices that would be difficult to discover without direct observation [Participant observers were provided with an observational guide to help describe and understand the food choice and eating patterns of ervation -38. Furtervation .One stream of coding identified household technology and its multiple uses. Standard uses and user adaptations were identified for each item. In a second stream of coding, the factors that interact with users and technological items were identified and categorized. A third coding stream involved the deductive identification of food insecurity status and other material hardships. The process followed a technique established and validated by Hamelin and colleagues  to deterTable colonia level. Food-related behavior was also influenced by biological and physical characteristics of the colonia setting such as vermin, wind, rain, heat, and cold weather.Categories of social group formation were associated with constraining and enabling the actions of women as they selected ingredients and dishes, and used food-related technology. These constraints and opportunities included conventional gender roles as home centered caretakers of children rather than wage earners, and the selection of ingredients and dishes common among Mexican-origin immigrants to the U.S. Distinct forms of material hardship were also identified: limited household financial resources and the built-environment at the household level, and limited neighborhood infrastructure and systemic poverty at the The mothers in this study were entirely of Mexican national origin, although many of the children were born in the U.S. All of the families described frequent interactions with family members still in Mexico, and many family members were currently dealing with the U.S. immigration process. Mexican-immigrant cultural repertoires were expressed through the dietary choices, culinary techniques, and tools used to prepare food. Foods and food practices were largely indicative of traditional Mexican foodways, although families had incorporated new foods widespread throughout both the U.S. and Mexico.fideo (pasta cooked in a chile inflected tomato broth), menudo (tripe and hominy stew), charro beans (bean soup), tamalestacosmole, and tortillas[molcajetes (mortar and pestle) to create soup bases from garlic, spices, and chiles; the charring and grilling of vegetables for salsas and soups; and tortilla making with a variety of presses.The observers recorded what they described as “typical Mexican food,” including regionally popular and traditional dishes such as tortillas. Foods ntortillas-47 inclufideo pasta, hotdogs, nixtamalized corn flour, wheat flour, and small quantities of low-quality ground meat. While better cuts of meat were mentioned, regionally popular meats and meat dishes were largely described as luxury items that were only featured on festive occasions. Meat and fish were not commonly consumed at home. In these households, socioeconomic status restricted regular opportunities to prepare desirable meat dishes and constrained the choice of ingredients and dishes to inexpensive staple items. Nevertheless, a cultural repertoire that took the form of dishes based on these inexpensive staples, allowed women for the most part to feed their families under conditions of material hardship. Another cultural repertoire was a fasting and feasting dynamic where regular meals were composed of inexpensive staples and bimonthly or monthly extended family feasts where meats were grilled outdoors on charcoal or wood fires. This repertoire allowed households the occasional opportunity to enjoy luxury foods.The foods most commonly prepared in these households demonstrate the interrelationship of constraint and opportunity present in the interplay between cultural repertoire and material hardship. The many inexpensive foods typically identified as common in Mexican-origin households present in these households represent a cultural repertoire. The six families that indicated the quality dimension of food insecurity relied heavily on the least expensive of these staple items. These ingredients included rice, beans, colonia homes. As observed elsewhere by Abarca [colonia life. These gendered cultural forms were made apparent through the performance of specific food-related technological tasks described in greater detail in the following section.Traditional gender roles were another constraint that shaped food-related technical practices within y Abarca  and Johny Abarca  the kitcy Abarca . A publicolonia households. At the household level, limited household resources curtailed residents’ capacity to acquire foods and household items, especially well-made, expensive, and specialized items. Income poverty also had an effect on the construction and condition of homes. The homes in this study were representative of self-build housing. Many were formed around a core trailer unit with additions. Construction of additions was also ongoing in a number of the homes.There were three categories of material hardship that shaped food-related technology use in colonia level, systemic material hardship often takes the form of limited availability of utilities within colonias. However, the colonias in this study had available water, sewer, drainage, and electrical services. Food related systemic hardship was expressed by the limited spatial access of all households to grocery stores and supermarkets, complicated by the limited availability of public transportation.Household indicators of material hardship are detailed in Table colonia homes is too lengthy to be reproduced here. The stages of this organizational structure are shown in Figure An organizational structure was developed to classify the uses of food-related technology. The complete list of items observed in these Acquisition of food involved a number of distinct techniques. Although no gardening was reported, two families raised chickens for eggs, and meat from animals such as chickens, goats or ducks. The predominant observed food source was the retail food environment. These outlets included grocery stores & supermarkets (eight families), convenience stores (six families), tienditas en casa  (two families), pulgas (flea markets) (two families), mobile fruit and vegetable vendors (one family), dollar stores (two families), mobile food vendors (three families), carnicerias (one family), bakeries (two families), fruit stands (four families), and tortillerias (one family). Food resources were accessed by walking to tienditas and convenience stores by three of the women, two entirely without vehicles and another without a vehicle during the week. They also asked friends and relatives to bring them items from grocery and other food stores. Households also relied on curbside service from mobile vendors of prepared foods and fruits and vegetables. Automobiles were used for more distant locations. Automobile use was common, although limitations in household resources were apparent in the condition of these automobiles. Many automobiles were in various states of disrepair, and residents often relied on friends and family for transportation. During the observational period, men performed all shopping, although all the women indicated they were regularly involved in shopping for food. The residents comfort with driving shaped this division of labor. One woman did not know how to drive and usually walked to the fruit stand and convenience stores. Her husband complemented this by shopping in his car.Storage was performed entirely by women. Once food entered the home, it passed into the feminine domestic sphere. Men returned with groceries, but they were delivered to women for storage or immediate preparation. Storage categories were cold, dry, secure, and frozen. The levels of material hardship, all of which inspired creative in-home adaptations, framed the understanding of the use of items within the home for storage. These included limited financial resources, limited linkages to neighborhood infrastructure such as water and gas, limited space, and the permeability of the home to vermin, heat, cold, wind and rain.colonia homes included refrigerators, freezers, shelving and cabinets, plastic jugs, and kitchen counters. The limited resources of the owners often prohibited their acquisition of specialty storage items. In response, all of the families improvised storage solutions.Common items used for food and beverage storage in Two families used broken refrigerators for dry storage. Plastic storage bags hung from walls were used for permanent storage of dried goods by three families , specifically for drinking water. This water was also used for cooking by three of the families.Neighborhood infrastructure impacted water consumption. All of the study homes had running water. The authors have no information on whether or not this water was safe to drink, although a number of residents clearly had strong preferences against drinking tap water, a preference shared with many residents of South Texas colonias. Five ofPreparation was largely the task of women, and a clear public/private or outside/inside task division was observed. Women prepared food within the home for family and guests. In four of the families, men were either observed or mentioned by women as preparing food, but only outside for barbecues where friends and family were served. One woman joked about how she tried to persuade her husband to help out around the kitchen to no avail; another described her husband’s rare offers of assistance as ineffective, and another spoke of her husband’s helpfulness cleaning around the house while she was nursing their newborn child.The use of tools in food preparation was largely the work of women. The use of kitchen tools was shaped by the three levels of material hardship, especially the limited resources available to obtain specialized tools. Also of importance were physical constraints such as the effects of inclement weather, and the preferences for specialized items designed to implement cultural repertoires such as the preparation of tortillas or other elements of Mexican cuisine.molcajetes (mortar and pestle)  (five families)  using wood or charcoal. The food cooked on a grill might be meat, fish, or grilled vegetables, but also included items often cooked on a stovetop such as beans.Limitations in household resources were exhibited through the use of alternatives to larger and more expensive pieces of equipment such as stoves, and the use of less expensive and more flexible forms of fuel. Three families had broken stovetop and oven combination units which were repurposed as storage units. Replacements included less expensive units such as electric hot plates or a two-burner gas unit. When one family ran out of money to purchase propane for their burner they chose to cook beans outdoors over an open fire. While it was not clear if this was entirely a matter of conserving propane or electrical utilities or simply preference, all of the families either described or were observed cooking outside on a grill, often repurposed from an old butane tank or hot-water heater  or sandwiches.colonias. The most common arrangement was a family seated in chairs at a table in the kitchen or living space. Other common arrangements included festive occasions such as family barbecues with meats and vegetables grilled outdoors. During these events, food would be consumed from a standing position around the grill. Indoor eating arrangements featured adaptations to limited space. One family in a home without room for an interior table and chair setting sat on a sofa and placed their food on their bed. Another family had room for a small chair and table setting with insufficient seating for the entire family. When this family dined together, many were seated on beds. Another family had a table and chairs in the living area adjoining the kitchen. This area was large enough for the children and the father to be seated at this table, but the mother and infant ate standing in the kitchen.Food consumption also entails the placement of food and the eater in convenient proximity. An eater dining at a table while seated at a chair is the normative case for many North Americans . A numbeCleaning is another category of practices constrained by the limited resources of the residents and the built home environment. Household cleaning was entirely performed by women. Cleaning was broken into three categories, personal hygiene, cleaning of food for preparation, and cleaning of the eating and food preparation areas. Brooms, mops, paper, sinks, paper towels, toothbrushes, and chemicals and soaps were all used for cleaning. Limited household resources inspired the adaptive use of a number of items. One home used a single functioning sink within the kitchen for cleaning vegetables and dishes, and for washing up after the bathroom and brushing teeth. Another used a piece of cardboard to clean instead of a dustpan. The limited availability of resources extended to the built environment. Few homes possessed a hot water heater, and stovetops were used to heat water to clean the home and for personal hygiene.Management of food waste is another practice that demonstrates structural constraints on the use of household technology. Three categories were developed to describe food-waste management: temporary storage, cleaning, and disposal. Overlapping with the storage category, temporary storage of food waste was primarily shaped by two conditions, limited family resources to purchase items for temporary storage, and limited space. Many families used plastic grocery store sacks to store waste. Due to limited space, some families stored waste from the kitchen and from the bathroom or other rooms in one location.Food-waste management was constrained by the lack of residential infrastructure and city services. Few residents had access to a trash pickup service. Some residents hauled their own trash to the city dump, but this was inconvenient and required a subscription to the city utility. Not all residents were able to provide this evidence, and not all had the time or the vehicle to deposit their own waste off site. These residents burned their waste.elotes (corn) that he sold throughout the neighborhood in his family’s mobile food business and then fed the husks to their animals. The father observed that his children did not like to eat their own animals, but they were comfortable with eating animals and eggs raised by their neighbors. This process is indicative of the flow of resources through the community, a process of reciprocal exchange with neighboring families that was undoubtedly present but only indirectly observed in this study.Not all food waste was discarded. Some food waste was fed to pets or to chickens, ducks and goats. For example, one father and his children first shucked the Colonias are archetypal examples of the new-destination Mexican immigrant communities now broadly dispersed throughout the continental U.S. [colonia residents is likely shared among women in other new destinations for Mexican immigrants, which bolsters the relevance of these findings.tal U.S. -10. The The collection of detail on technological and other material household constraints is of importance when considering how household members cope with food insecurity. Material hardship is a useful conceptual linkage between food insecurity and other household demands including the material needs identified in this study. The satisfaction of demands for a secure food supply, food-related technology, medical care and insurance, clothing and other material necessities requires the application of economic or alternative resources. In impoverished households these demands may outstrip available resources and families may be forced to choose between material necessities. Thus, the concept of material hardship which has taken a prominent role in the sociological and demographic literature on poverty ,53,54 shObservations of eating arrangements that used beds and sofas for seating and as tables resembled arrangements described in limited-space low-income dwellings in British households by Charles and Kerr  and MexiA number of practical considerations can be derived from examining food-related technological practices in the home food environment. Acknowledging these practices may impact nutritional interventions. For example, eating with a tortilla or a spoon implies a technological distinction that will likely influence caloric intake. Researchers that wish to capture and positively influence the consumption patterns of Mexican-immigrant communities must come to some understanding of what tortillas mean as a utensil for overall consumption patterns.colonia residents to cope with material hardship, this paper adds to the recent conversation among cultural sociologists of how cultural repertoires are shaped by social and material circumstances [colonias.One of this paper’s strengths is the exploration of strategies for coping with material hardship as cultural repertoires. By identifying the ingredients, dishes and technological practices employed by these mstances -27,32. Ipromotora-researchers who served as cultural brokers and lessened the distance between university based researchers and community members. The promotora-researchers collected high quality data and provided intimate observations of the households, permitting access to otherwise inaccessible day-to-day household activities.This study also possessed methodological strengths including the use of participant observation , a novelcolonia households.This research was not without limitations. The observations were performed in the winter. Observations collected across multiple seasons would have allowed a broader categorization of the factors that impacted food-related technological behaviors. The sample also was of a small number of households in one region of South Texas and conducted over a single month, and can thus not be described as capturing the entire breadth of food-related technological practices or forms of material hardship to be seen among South Texas colonia households in this study evidenced forms of material hardship including limited space in their homes; poor health conditions; limited insurance and health care access; inadequate housing, and food insecurity. To adapt to these conditions, women colonia residents creatively employed cultural repertoires including the dishes and inexpensive staple ingredients of regional cuisine, and their limited and multipurpose forms of kitchen technology. In colonia households, women expressed a creative capacity to acquire, store, prepare, feed and eat, clean and dispose of food waste that was nevertheless structured by the constraints endemic to their status as women Mexican-immigrants residing in households/homes and neighborhoods constrained by material hardship.The The authors declare that they have no competing interests.JRS conceived and designed the study. WRD analyzed data. WRD, JRS, CMJ and JSJ contributed to data interpretation. WRD prepared the first draft. WRD, JRS, and CMJ made revisions, JSJ supervised and conducted data collection, and all authors read and approved the final manuscript.


The apoptotic pathways, respectively, intrinsic or extrinsic, are executed through molecular signals travelling inside the cells. If the initial studies considered the nucleus, and specifically DNA, as both primary sensor and executioner of apoptosis, active roles of other intracellular organelles have been pointed out in the last two decades, identifying plasma membrane as the initiator of the extrinsic pathway and mitochondria as the pivot of the intrinsic pathway. In apoptosing cells, the outer membrane of mitochondria is permeabilized by the proapoptotic members of the Bcl-2 family, promoting the release of proapoptotic factors such as the primary and secondary activators of caspases . Stress signals, typically inducing the intrinsic apoptotic pathway, must be perceived by the damaged cells and translated into signals that promote mitochondria permeabilization, after which caspases are activated. This implies that other organelles participate in apoptotic signaling upstream to mitochondria involvement, acting as sensors of damage or signal transducers. Recently, a key role of the endoplasmic reticulum (ER) is emerging, consisting of the ability of amplifying or dampening the apoptotic signal prior to mitochondria involvement, through the establishment of active Ca2+ fluxes that control the physical and functional interaction between mitochondria and ER. Also lysosomes participate to the intrinsic apoptotic signaling, and their dialogs with mitochondria have been described. Other important examples of organelles cross-talk in apoptosis include nucleus-mitochondria exchange of proteins such as p53, which is main controller of the cell response to DNA damage. To date, the role of organelles other than mitochondria in perceiving and signaling cell damage, and the interrelation of the organelles during apoptotic signaling, are still poorly explored matters.Apoptosis and survival pathways are intimately connected signal transduction cascades that determine the fate of cells suffering from insults such as DNA damage, oxidative stress, intracellular CaIn this special issue dedicated to Organelle Cross-talk in Apoptotic and Survival Pathways, original research papers and review articles are collected with the aim of giving an impulse to this promising field of research on apoptosis and stimulating discussion between interdisciplinary readers.2+ signaling between these two organelles and control bioenergetics, cell survival, but also cell death decision.The paper written by Y.-B. Ouyang and R. G. Giffard describes ER-mitochondria cross-talk during cerebral ischemia. The authors precisely describe the chaperone machineries at both the ER and mitochondrion. Moreover, they contribute the new view that the chaperones organise not only the regulation of CaMitochondrial dynamics: functional link with apoptosis”, written by H. Otera and K. Mihara, the readers are introduced to “intrinsic” apoptotic pathway in the context of regulation and physiologic significance of mitochondrial fusion and fission. The authors of this review underline also that the ER-mitochondria contact is involved in the regulation of mitochondrial energy, lipid metabolism, calcium signaling, and even in mitochondrial fission.In the paper entitled “An important issue arising is the cross-talk of apoptosis with autophagy, a stress response pathway controlled by key intracellular regulators such as m-TOR, induced by insults or conditions ranging from nutrient depletion, protein malfolding, or cell ageing. The paper written by H. Rikiishi focusing on the recent advances regarding autophagy in cancer and the techniques currently available to manipulate autophagy. The author of this paper provides a complete overview of the literature on molecular mechanism of autophagy and its cross-talk with apoptosis. Additionally, the author indicates the technical problems in the study of autophagy and suggest that new methods need to be developed to ensure progress in this area of investigation. Moreover, they highlight that the multifaceted nature of autophagy and its diverse cross-talk with other biological processes must be carefully considered when the autophagic system is targeted for anticancer benefits. Effects of cisplatin in neuroblastoma rat cells: damage to cellular organelles” written by G. Santin et al. provides the practical analysis of organelle cross-talk during cell death. The authors indicate that B50 neuroblastoma cells treated with cisplatin undergo apoptosis through organelles injury, and not only as a consequent of DNA damage, but also that cisplatin does not induce any autophagic process as alternative response to the treatment.The paper entitled “In conclusion, the studies collected in this issue effectively contribute to the general problem of organelles as target of cell damage versus transducer of the apoptotic signal.Lina GhibelliLina GhibelliAlina GrzankaAlina Grzanka


Pandemic influenza  has ravaged the health scenario worldwide. ResourceThe containment of the pandemic in India was possible only by the prompt and efficient measures taken up by the Government of India. Immediately after cases were reported in Pune, Maharashtra, and other places all over the country, steps were taken to chalk out guidelines for control of the disease in India. Isolation of the cases in the healthcare facilities and home environment (depending on severity of illness), categorization of cases, providing treatment to suitable individuals (cases and household contacts), public education, and other appropriate measures have proved very effective in due course of time.Healthcare authorities in India have developed a strategy of categorization of patients  in threeLaboratory testing, under this strategy, was conducted in patients belonging to Category-C; treatment with anti-viral drug Oseltamivir was, however, restricted to severe cases only, even if they were not lab tested. Among those tested, 94% of cases were found to have recovered Figure . In addiA valid observation that is made from the data on laboratory testing is that a large majority of those individuals who were tested  have been declared negative for the virus . One of Several factors were observed to be associated with increased morbidity and mortality. These can be broadly grouped under four categories: those pertaining to (a) diagnostic factors (b) evaluation of severity of illness (c) management issues, and (d) delivery of care.Issues pertaining to diagnosis were mainly clustered around the following factors: (i) lack of access to health care – mainly in remotely situated pockets in the interior regions; (ii) seeking care from traditional healers like village doctors/registered medical practitioners; and (iii) varied clinical picture of the disease  to acute lung injury and acute respiratory distress syndrome in some individuals); (iv) the high prevalence of confounding and/or co-infecting illnesses like malaria, dengue, chikungunya and other viral illness often vitiates the clinical picture and creates a diagnostic confusion. Viral co-infection demands testing for multiple viruses and may be associated with an increase in morbidity and mortality; (v) a large prevalence of associated chronic illnesses like tuberculosis, kala-azar, malnutrition, etc. Such illnesses may predispose the patient to acquire ILI.Another impediment to early diagnosis is the lack of any rapid, point-of-care diagnostic tool. The rapid influenza diagnostic tests (RIDTs) have sensitivity between 20 and 90% as compared to RT-PCR and vial culture. The sensitivity depends on age, duration of illness, sample type, and viral strain.The various factors pertaining to poor assessment of severity of illness are as follows. Firstly there is largely a poor assessment of cases at the primary care level. Innumerable cases of delayed referral to higher centers, resulting from delayed recognition of acute hypoxemic respiratory failure (ALI-ARDS) have been observed. A possible solution may include proper training of healthcare personnel at primary healthcare centers/sub-centers, community health centers, and district hospitals. Provision of simple and cheap monitoring devices like finger-probe oximeters may also be considered as a useful measure to overcome non-availability of simple tools to assess oxygenation status. A lack of clinical and laboratory markers which can predict serious forms of disease, particularly in patients without co-morbidity, is also a handicap. It may be added that unlike many other illnesses, there is no validated, severity assessment score, specific to influenza that is available to clinicians till date.All these factors may often lead to a delay in referral to the hospital by peripheral centers, resulting in late initiation of treatment and higher mortality.There are several issues relating to drug therapy that need to be considered. Antiviral therapy with Oseltamivir was given only to all high-risk and seriously ill patients under the Govt. of India strategy. In addition, prophylactic treatment was given to high-risk contacts of all seropositive patients. Not treating patients with mild disease did not seem to have any adverse impact on the outcome of the epidemic in India. It is also noteworthy that due to non-availability of intravenous preparations of Oseltamivir and other drugs, difficulties were often faced in treating patients on ventilator who had a non-functional gut.In the absence of clear-cut guidelines with regard to maximal drug dose, maximal prolongation in duration of treatment and combination of multiple of anti-viral drugs etc, extensive variability in management patterns have been observed amongst physicians.As far as healthcare delivery is concerned, it has been observed that there may have been cases of delay, particularly in referral of cases to higher centers and institution of specific supportive treatment. As mentioned earlier, lack of adequately trained manpower may be a contributing factor. Also, there is a dirth of adequate number of high-dependency units and intensive care units, specially dedicated to management of pandemic influenza. This is particularly so in the peripheral and interiorly located regions. A large number of isolation ICUs were created in major hospitals at the initiative of Ministry of Health and Family Welfare, Govt. of India. These units have successfully managed seriously ill influenza patients. Fortunately, the overall severity of the epidemic was generally mild this time. However, if the next wave of the epidemic is more severe, there would be a need to significantly enhance the availability of ICU and HDU beds.The socio-culture milieu in our country offers a perfect setting for the re-assortment of the pandemic influenza virus. Rural India has the human host, poultry birds, and the pigs sharing the same premises for habitation in close proximity. As predicted by public health experts, the scourge of the pandemic is far from being over. In such circumstances, developing countries like India would, therefore, be fertile grounds to bear the brunt, in case of resurgence of the disease.In the backdrop of the aforementioned facts, some remedial measurements may always be suggested. Development of community-based modules must aim at optimizing treatment at the primary care level with a focus on early evaluation of severity of illness, provision of early and effective treatment so as to bring about a decrease in morbidity and mortality. Workshops may be arranged to train primary care physicians in early diagnosis, endotracheal intubation, oxygen therapy, and non-invasive ventilation. High-dependency units may be installed and made functional at district-level hospitals. Mobile ICUs may be provided and access to expert critical care physicians be extended by telemedicine, telephone hotlines, and Internet. Websites and webcasts to disseminate knowledge about pandemic influenza cases may be very useful.With the vast data at our disposal, several areas of research can be identified. Studies to find out the clinical profile, severity, complications, and the co-morbidities are required. Based on the audit of hospitalized patients, clinical and biochemical markers which can predict the development of serious disease should be studied. Particular mention is made about issues related to development of intravenous preparation of anti-H1N1 influenza drugs, studies to assess the ideal infection control measures in ICU (role of different types of cost-effective masks), bronchoalveolar lavage fluid, lung biopsy specimens, and post-mortem specimens in the understanding of pathophysiology and pathogenesis of the disease and further genetic research for identifying high-risk groups. This issue of Lung India contains articles covering some of these aspects.–14


The application of post-genomic techniques in plant respiration studies has greatly improved our ability to assign functions to gene products. In addition it has also revealed previously unappreciated interactions between distal elements of metabolism. Such results have reinforced the need to consider plant respiratory metabolism as part of a complex network and making sense of such interactions will ultimately require the construction of predictive and mechanistic models. Transcriptomics, proteomics, metabolomics, and the quantification of metabolic flux will be of great value in creating such models both by facilitating the annotation of complex gene function, determining their structure and by furnishing the quantitative data required to test them. In this review, we highlight how these experimental approaches have contributed to our current understanding of plant respiratory metabolism and its interplay with associated process . We also discuss how data from these techniques may be integrated, with the ultimate aim of identifying mechanisms that control and regulate plant respiration and discovering novel gene functions with potential biotechnological implications. Metabolism represents one of the most important and most likely the best characterized network within biological systems. From pioneering studies defining key metabolic pathways, subsequent decades of enzymology characterizing the catalytic and regulatory properties of enzymes, through to more recent genetic studies of metabolism, there is an unprecedented density of both mechanistic and descriptive data relating to metabolic behavior. Advances in the understanding of metabolic regulation and control, however, still suffer from insufficient research concerning the mode of operation of metabolic networks, and plant respiratory metabolism provides an illustrative example of this problem. Due to the crucial roles of mitochondria in meeting the energy demands of the cell whilst simultaneously being involved in amino acid metabolism and photorespiration, precise control of mitochondrial metabolism and function is crucial for cellular homeostasis, and unsurprisingly mitochondrial dysfunction leads to diverse metabolic and phenotypic consequences . HoweverGiven the complex patterns of regulation and the interactions between respiratory metabolism and other processes uncovered by such studies, it is likely that only through the use of model-based approaches we will be able to understand how the individual components of metabolism  work together to produce a functioning system, and in this way truly understand the function of individual components of that system. In this context systems biology offers the promise of a better understanding of respiratory metabolism and its role within the metabolic network.Systems biology aims to understand how populations of molecules, cells, and organisms interact to give rise to complex biological processes, including cell division, growth, development, metabolism, and behavioral and ecological patterns . AlthougIn the case of plant respiratory metabolism, whilst the core components, including enzymes of the TCA cycle and components of the mitochondrial electron transport chain, have been identified and characterized in numerous species , how theTable 1; Figure 1) has increased our ability to annotate gene functions within plant respiratory metabolism, obtain quantitative data and uncover unanticipated relationships between respiration and other cellular processes such as photosynthesis, photorespiration, redox regulation, and signaling  expression in Arabidopsis, has also been investigated using transcriptomics. Such plants, when grown in moderate light under drought conditions, displayed 10-fold increases in leaf anthocyanin levels, together with alterations in photosynthetic efficiency, increased superoxide radical production, and reduced root growth  has renewed the use of 2-D gels for quantitative comparisons of the mitochondrial proteome. Studies using DIGE have investigated knockout mutants for carbonic anhydrase-like proteins , complexbidopsis  and ricebidopsis . These sArabidopsis in particular has been extensively analyzed by both gel-based and gel-free strategies , introducing side activities to plant complex I, while all the remaining nine subunits are rather small (7–12 kDa) and of so far unknown function  complex in tomato led to alterations in whole plant development that were linked to reductions in total amino acid and nitrate pools despite unaltered photosynthesis . These rAntisense inhibition of the iron–sulfur subunit of the SDH in tomato plants, on the other hand, resulted in increased photosynthesis and whole plant biomass via an organic acid-mediated effect on stomatal aperture. These results contrast with those obtained for antisense inhibition of fumarase, where decreased photosynthesis and biomass were observed . FurtherD-2-hydroxyglutarate dehydrogenase provide electrons to the plant ubiquinol pool via the electron transfer flavoprotein (ETF)-ETF:ubiquinone oxidoreductase (ETF/ETFQO) complex  spectroscopy it is possible to determine both enrichment and location of incorporation of label in individual metabolites without laborious chemical cleavage. This method was used to investigate the fate of BA shunt . Additiocle flux , most li2 released by respiration  are expected.Whilst investigation of the transcriptome, proteome, and metabolome alone may be highly informative, cellular physiology and the regulation of plant respiratory metabolism is the result of complex interactions between transcripts, proteins, and metabolites. Bearing that in mind straightforward relationships between these components of the metabolic network are therefore not to be expected. Thus, despite the apparent easy understanding of simple relationships between changes in transcripts, proteins, metabolite, and downstream biological functions, quite often there is a major discordance. This apparent discrepancy can often be explained by quantitative analysis of the data sets and information about translational regulation and protein turnover. These incoherencies are not only due to technical issues but also related to the complexity and structure of metabolic networks. Accordingly, some priorities in metabolic research to reduce these problems have recently been proposed . For thiArabidopsis  will additionally allow a fuller description of the metabolic status of a plant. When this is achieved, global analyses of RNA, protein, and metabolites will allow us to obtain a full picture of the complexity of the system under study. Although the application of these techniques requires substantial financial investment, it is likely to bring returns in the form of an improved ability to carry out rational engineering of the plant metabolic network.Overall, whilst post-genomic technologies have already aided our understanding of respiratory metabolism at a systems level through additions to the “parts list” of the metabolic network , they arThe 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.


Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research. Evolutionary development biology (evo-devo) is concerned with how developmental systems evolved, while probing the consequences of these historically established systems for organismal evolution . ResearcModern lifestyle and medicine have influenced nutritional and infectious constraints on puberty, resulting in the secular trend in pubertal development over the past 150 years. In girls, more than in boys, the change in pubertal age has been intriguing; in the last decades, the rate of precocious sexual maturation in girls has been high and increasing, and the mechanism for the 'epidemic' has been much debated, pointing fingers at toxins and perhaps other chemical products. Evidence that the timing of boys' somatic maturation is changing has recently been reviewed and remains inconclusive , though homo sapiens there has been much change in the timing of pubertal maturation - and not just in a singular direction - and a variety of contextual factors appear to regulate pubertal development. To our way of thinking, it is a mistake to focus only on environmental toxins or even simply cast changes in pubertal timing in disease terms.Evolutionary analysis highlights the fact that it is the female who is reproductively constrained in terms of the maximum number of offspring she can generate over her reproductive years. In consequence, early maturation affords a potential fitness advantage for females more than males, allowing more time to reproduce. Thus, evolutionary life-history thinking challenges the prevailing notion that early puberty is exclusively or primarily pathological in origin, viewing it rather as an adaptive response to changing life conditions. Indeed, as we hope to show, evidence indicates that since the emergence of We challenge the pathological view by advancing an evolutionary perspective on the issue of juvenile transition and timing of pubertal development, as drawn from life-history theory. Toward this end we consider the anthropological record, showing that adolescence as a stage was a new development in primate life history and that over time there have been many changes in pubertal timing, both accelerating and delaying it. While acknowledging heritable individual differences in pubertal timing, we emphasize developmental plasticity and the role of the environment in regulating pubertal timing in the service of fitness goals, using hormonal and developmental mechanisms. A central claim will be that the transition from the preceding stage of juvenility to adolescence entails adaptive developmental response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood, with the latter defined as the life-history stage of reproduction Table . The plaEvolutionary life-history theory deals with the strategic allocation of an organism's energy toward growth, maintenance and reproduction, including raising offspring to independence, while avoiding death ,5. It prRelative to other species, human life-history strategy includes a long period of postnatal growth, including dependency to sexual maturity, rapid adolescent growth and delayed reproduction . ConsideThe terms puberty and adolescence are often used interchangeably and thus incorrectly. Whereas puberty refers to the activation of the neuroendocrine hypothalamic-pituitary-gonadal axis that culminates in gonadal maturation and the biological effects of sex steroids, the package we call adolescence includes such pubertal development plus the growth spurt, cognitive and brain maturation, and social aspects in learning, intimacy and mutual support, intensification of pre-existing friendships, development of new relationships, and the attainment of biosocial skills needed for successful reproduction. The collective endpoint of the adolescence package is the socially and reproductively mature adult. To promote reproductive and parenting success in the service of reproductive fitness, hormonal and mental maturations are intimately coupled through iterative transactions between the nervous system and endocrine systems, with the latter involving gonadal steroid hormones .Australopithecus afarensis had only three postnatal, pre-adult life-history stages, just like the chimpanzee - 5 years of infancy, 5 years of juvenility and 2 years of youth - before the onset of reproduction [Homo sapiens [As late as 3,000,000 to 4,000,000 years ago the early homininae  sapiens : infancyThe uniquely human adolescent growth spurt is often regarded by physical anthropologists and ape biologists as the operational definition of adolescence , even thIn addition to being a period of rapid growth, adolescence is a time of subcutaneous fat deposition, especially in girls. Whereas subcutaneous fat is evenly spread over the female chimpanzee's body, the human adolescent has striking fat deposits in the thighs, buttocks and breasts, even if she is thin overall. These enable her to get through periods of scarcity, signal sexual maturity and facilitate sexual attraction of a mate, and allows others to continuously monitor her nutritional state .Boys and girls embark on different come-of-age strategies to achieve their fertility goals Table . The onsFrom this time forward, girls have an apparent womanly body form, yet are not fertile; they will develop an adult cycle of ovulation and adult size of the birth canal much later, around 18 years of age. They gain knowledge of their adult social roles while still infertile, but perceived by adults as mature. The perception of fertility in girls facilitates their entry into the social-economic-sexual world of adult women, allowing them to practice reproductive skills without conceiving .Boys show a pattern of gradual maturation of the hypothalamic-pituitary-gonadal axis similar to that of girls, becoming fertile at 14 to 15 years on average, about two years after their peak height velocity. But they are still young in outward development, body size, voice and facial features. Boys will learn their adult social-economic-sexual roles while already sexually mature but not yet perceived as such by adults. This allows them to interact and learn from older adolescents and adults without seeming to compete for status and other important resources, including fertile females ,13. TestAll mammals, including the great apes, transit directly from infancy to juvenility without passing through the childhood stage - except humans Figure . CompariWe and others have defined juvenility as a distinct life-history stage in humans, characterizing it in terms of endocrine and body composition changes resulting in changes to social assignments and psychological maturation ,17. DeveDel Giudice contends that juvenility (adrenarche) represents a 'switch point', a time when the environment can reprogram nascent reproductive strategies established earlier in life ,20. IndeIn social terms, juvenility offers opportunities to prepare for the social complexities of adolescence youth and adulthood - in part by assaying one's social status and standing in the competitive world of peers . TransitHomo erectus imply increases in lifespan and delayed adrenarche and reproductive maturation, and as such are a natural point at which to consider the potential role of delayed transition from childhood to adrenarche in human evolution.The age at transition from childhood to juvenility has been remarkably constant, especially when compared to the plasticity that characterizes other life-history features such as age of sexual maturation . CompariAge and size at adolescence have strong effects on an individual's fitness because they affect reproductive potential, schedule and efficiency . EmphasiSubstantial physiological variation of some 4 to 5 years is evident for age at onset of sexual maturation across individuals under varying life conditions . DespiteThe human population has grown exponentially from a brink of extinction 80,000 years ago, with a world population of several thousands, to that of several billion today. Such population growth increased opportunity for genetic mutations, thereby accelerating the pace of human evolution . EstimatDevelopmental and maturational tempo is flexible and responsive to environmental conditions in a presumptively adaptive manner. When immature animals experience severe environmental stresses such as malnutrition or disease, maturation is often delayed until conditions improve and normal growth can resume. By contrast, when animals are raised under ideal conditions that promote rapid growth, internal checkpoints ensure that maturation does not occur until juvenile development is complete. But when contextual stress is not so great as to challenge survival, pubertal development is accelerated, thereby increasing the likelihood of reproduction before death or disability. Collectively, these phenomena highlight a U-shaped link between contextual risk and nutritional cues as they predict pubertal development Figure . NutritiDomestication of animals and agriculture altered the human environment - and, thereby, human development - in several ways, including adaptive changes in the onset of puberty. A relatively sedentary lifestyle increased local human densities, facilitated the spread of infectious diseases and was associated with recurrent famines. Later maturation to adulthood was a tradeoff to adapt to poor nutrition as well as the increasing complexity of being an adult in a society engaged in agriculture, settlement and population aggregation. Increased differentiation of social tasks and the creation of societal hierarchies in wealth-accumulating agrarian societies resulted in variation in nutritional status and family conditions, which themselves led to an overall increase in the mean age of menarche. This crucial point is further discussed below under 'Evolutionary Theory of Socialization'. Thus, by medieval times, the average age of menarche was deferred to 16.5 years, as it remains today among underprivileged adolescents in developing countries .Modern hygiene and medicine have influenced nutritional and infectious constraints on puberty, resulting in the secular trend in pubertal development over the past 150 years (see below). Further evidence to this effect would seem to come from research showing that girls and, to a lesser extent, boys adopted from developing to industrial countries show accelerated sexual development ,42. The th percentile, showing an early juvenile deceleration, early pubertal spurt and early growth termination [The Philippine Aeta provide unique insight into the strategic importance of the age of adolescence. Their growth deviates from the U.S. 0.01mination . With limination .The secular trend provides compelling evidence that pubertal development is developmentally plastic. Over the past 150 years - without any documented change in gene frequencies - the age of menarche has fallen by a full 4 years in the industrialized West . Considview see , and thaview see . Importaview see , and thaview see .In line with the above, experimental manipulation of licking and grooming of newborn rats by their mothers illuminates the role of epigenetic processes in regulating the stress-response system, pubertal timing, sexual behavior and parenting , as reviSome individuals are more plastic and responsive to environmental cues and others less so, adopting a more fixed developmental trajectory for reproductive strategy ,57-62. CThis review uses an evo-devo approach and life-history theory for understanding human adolescence and especially variation in the timing of reproductive maturation. Developmental and maturational traits that respond to environmental cues enhance fecundity-survival schedules and behavioral strategies that yield the highest fitness in a given environment.Why is it that we have a unique adolescence phase, preceded by a juvenile phase and followed by a youth phase leading to such a delayed reproduction? Like other organisms, humans evolved to withstand environmental hardships by responding in ways that maintain evolutionary fitness, even if submaximal. The means to do this is a series of predictive adaptive responses that utilize the sensitive times of transitions from one life-history stage to the next, each assigned with its own domain. The transition from juvenility to adolescence is deferred when food supply is short, programming at the same time for later fecundity and fertility and for longevity ,66.Homo's evolution is genetic, the gradual secular trend in industrial societies over the last 150 years is not, given the short timescale. The more recent tendency for earlier puberty reflects the overall quality of modern environments, allowing females to approach the extremes of their genetic range of reaction. Such evo-devo thinking demands reconsideration of the notion of 'precocious puberty'. This term implies pathology, whereas the vast majority of early puberty probably reflects normal physiological and adaptive developmental plasticity [The timing of puberty sheds light on the relationship between phenotypic adaptive plasticity and adaptive genetic changes. Whereas the gradual tendency to mature late over asticity . Thus, tThe implications of disconnection of the mental and somatic components of human adolescence are underappreciated, and result in both mental and somatic consequences. Among them are the obesity and polycystic ovary syndrome epidemics, but also mental and social behaviors. In an American study, early-maturing girls displayed higher levels of self-reported criminality, drug abuse, social isolation, early sexual behavior and psychiatric problems . Early-mHereditary, environmental and stochastic factors regulate puberty in a unique environment, but their relative contribution to the phenotypic outcome and the extent of stochastic epigenetic reprogramming that is required to alter human phenotypes is not known because few data are available . If the Perhaps the most fundamental question raised by the life-history approach to adolescence concerns the uniqueness of each child in her given genetic background and current environment as they best serve her reproductive fitness. Given the evidence on the strong influence of socioeconomic conditions early in life, we have to better understand how these interact with or via endocrine mechanisms to generate signals that affect life history and adolescence.DHEA: dehydroepiandrosterone; DHEAS: dehydroepiandrosterone-sulfate.The authors declare that they have no competing interests.Both authors conceived of the article and wrote it. Both authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/113/prepub


Vaginal biopsies and smears were collected from ten adult local healthy goats. Routine histological methods were carried out on vaginal biopsies and then stained with PAS stain. The smears were stained with Methylene blue. All samples were inspected under light microscope. The present study found that many constituents of the wall of the vagina, which have an important functional role, were absent; among these were the vaginal glands, goblet cells, muscularis mucosa, and lymphatic nodules. On the other hand, vagina showed special compensatory histological mechanisms, namely, the deep epithelial folds, the well-developed germinated stratum basale, the apparent basement membrane, and the profuse defensive cells, such as neutrophils, macrophages, lymphocytes, plasma cells, and mast cells. The general stains of this study could not recognize dendritic cells although they play an important functional role. Moreover, the herein study declared also that the vaginal smears showing many adaptive cellular mechanisms among these were, the keratinization, the process of sheet formation that lines the vaginal lumen, the process of metachromasia which is related to the cellular activity in protein synthesis, keratin, and finally the presence of endogenous microorganisms. It was concluded that all the above cellular compensatory adaptive mechanisms may compensate the lacking vaginal constituents and act to raise the immune response of the vagina. The application of vaginal cytology as a useful tool for estrus detection in modern breeding stations has been described for some species and breeds of animals . The patOn the other hand the cytological picture of vaginal smears was greatly affected by ovarian hormones . Under tμm sections were prepared for staining with Periodic Acid-Schiff reagent (PAS) stains [Vaginal biopsies were done on ten healthy local adult goats during spring 2012. This experiment was carried out in animal's farm, College of Veterinary Medicine, Baghdad University. Samples were fixed immediately by neutral buffered formalin 10%, and routine histological processes were done. Each specimen was embedded in paraffin, and 5–7 ) stains . The vag) stains . BiopsieThis study found that, as other animals do, the vaginal wall of the goat lacks glands, muscularis mucosa, lymphatic nodules, and goblet cells. In response, many adaptive compensatory structural changes were observed, namely, cytological and cellular adaptations, leukocytes infiltration, and microflora deposition. The current results declared that the vaginal mucosa showed numerous deep folds , well-deThe cytology of vaginal exfoliation had been described in the goat , 2. The Glands arise during fetal life by means of proliferation and invasion of the epithelial cells into the underlying tissue, followed by further differentiation . The preMuch controversy had been reported about the basement membrane in the vagina. Many authors neglected the referring to the basement membrane . Other aThe abundant engorged blood vessels present in the underlying tissue demonstrating the rich blood supply to the vagina. These blood vessels supply metabolites, vitamins, growth factors, antibodies, and phagocytized cells . Heavy iThe importance of keratinization was to protect the vaginal epithelium from invasion of microorganism. This finding coincided with  who repoThe herein result demonstrated that the cellular sheet formation and the intercellular communications have an important role in raising the cellular adaptive response, by obliterating the spaces between the vaginal epithelial cells to prevent the penetration of materials and invasion of pathogens between the cells and the underlying tissue. This agrees with the finding of  about keEndogenous bacteria metabolize the glycogen into lactic acid leading to decreasing the pH of the vagina and protecting it from pathogenic bacteria. This confirms the finding of , 34, 35.This result found also that the cytoplasm and nuclei of the vaginal epithelium undergo metachromasia, through which the tissue colour shifts from blue to red or purple. High concentrations of rough endoplasmic reticulum exhibit cellular metachromasia which is important in synthesis of the protein and keratin during the process of keratinization. This statement is in accordance with the result of  which stThe recent study referred to the relationship between the affected keratinized apoptotic vaginal epithelial cells and the phagocytizing neutrophils. This is confirmed by  which reAlthough the relation between structure and function is now well understood, much remains to be discovered about how the cellular components of any organ interact with one another. As structure follows function, the special location and the type of function of the vagina lead to deterioration and adaptation of its components to overcome the functional need. Cells and tissues form and cope according to their location and functional demand as the same cell type can exhibit different characteristics and behaviors in different regions and circumstances.


This series provides an important opportunity to consider how diagnostic pathology autopsy could be used in conjunction with verbal autopsy to provide more accurate cause of death and mortality data in all countries, and specifically in those countries with inadequate or nonexistent death registrations systems. For the purposes of this commentary, the term "autopsy" will denote the medical-pathology diagnostic procedure, in contrast to "verbal autopsy."The term "autopsy" means "to see or observe for oneself," but traditional use has been reserved for the postmortem examination of a (dead) body by a physician/pathologist, in order to identify diseases and injuries and determine the cause(s) of death. This medical-diagnostic pathology procedure integrates trained observation of the external and internal body with dissection or other invasive procedures, in order to obtain tissue samples, which are evaluated by microscopy and other specialized laboratory modalities, including chemical, toxicologic, genetic, and molecular biologic analyses. Used more broadly, the term "autopsy" reflects the aggregate of procedures used for postmortem medical diagnosis or death investigation, including investigative procedures that identify information about the deceased's medical history and the circumstances and scene of his/her death.To most pathologists and physicians, the term "verbal autopsy" seems a contradiction in terms. However, it is a clearly defined procedure, which allows classification of cause of death and cause-specific mortality by the analysis of data derived from structured interviews of family, friends, and caretakers, as well as review of any available medical records . As moreThe accuracy of verbal autopsy depends in large part on the quality of the diagnostic criteria, as well as on the age of the deceased and the type of diseases that are involved. Deaths associated with nonspecific signs and symptoms are especially problematic. The recent controversy about malaria mortality in India was a newsworthy example of the difficulty of differentiating malaria-caused deaths from those due to other febrile illnesses, such as septicemia, meningitis, encephalitis, and pneumonia . Other aDiagnostic pathology autopsies have long been considered the "gold standard" for cause of death determination. Although autopsy rates are generally low in many developed countries, estimated at less than 5% in US hospital deaths, studies have continued to demonstrate substantial discordance between clinically- and autopsy-determined causes of death despite technologic advances in diagnostic modalities. These discrepancies are reflected in both clinical records and death certificates. Major diagnostic error rates involving the primary cause of death have ranged from 10% to more than 30%, even in a recent study that suggested a decline in the autopsy detection of unsuspected diagnoses -8.Autopsy-based studies of cause of death in Africa have also confirmed a high rate of diagnostic discrepancy. In a population-based autopsy study of HIV-1 infected gold miners, discrepancies between clinical and autopsy diagnoses were high, with 51% of infections and 55% of pulmonary tuberculosis diagnosed at autopsy having been missed clinically . A studyA major advantage of a diagnostic autopsy is that it can identify a cause or causes of death based on pathologic tissue diagnosis. Even in deaths in which pathologic examination does not identify a definite cause of death, that information can be integrated into the death investigation process to guide the performance of additional studies and the formulation of the most likely cause of death based on all available diagnostic information. Autopsy also identifies chronic and infectious disease processes that may not be the direct cause of death, permitting assessment of prevalence for these processes. Another advantage is that the creation of tissue repositories by preservation of tissue for histologic studies may facilitate later disease discovery and characterization, allowing modification of mortality data based on medical scientific advancement.A major impediment to the performance of diagnostic pathology autopsies is the requirement for trained pathologists and assistants and histologic laboratory infrastructure for processing tissues for microscopy and preserving tissues, not currently available in many low- and middle-resource countries, particularly in nonurban settings. However, compared with many diagnostic modalities, such as those required for radiologic imaging, autopsy is a relatively low-tech and inexpensive procedure, which utilizes the same clinical and anatomic pathology laboratory resources needed for the provision of quality medical care in these settings. Another concern is the impact of cultural and religious attitudes about death and the handling of dead bodies. As this varies by country, culture and religion, this issue will need to be addressed on a case-by-case basis. Education, discussion, respectful communication and practice, and modification and limitation of invasive procedures for community acceptance could contribute to acceptance of this postmortem diagnostic procedure.Verbal autopsy is a valuable indirect system for establishing cause of death and cause-specific mortality, but like any clinical and historical investigation, it will misclassify a substantial number of deaths when compared to the true "gold standard" for death classification, diagnostic pathology autopsy. Too many natural disease processes have similar presentations, symptoms, and signs, and the same assumptions that result in inaccurate cause of death determination in up to 40% of physician-certified deaths will be present in verbal autopsy data. What is now needed in low- and middle-resource countries are robust studies of the concordance of verbal and diagnostic pathology autopsy to assess the contribution that diagnostic pathology autopsy can make to the quality of verbal autopsy and other mortality data. Similar studies would also be valuable in developed countries with reportedly high-quality cause of death data. Continuous evaluation of a proportion of deaths by diagnostic pathology autopsy in conjunction with verbal autopsy could promote continuous quality assessment and improvement of mortality data, and at the same time facilitate the identification of new or emerging disease processes.CLF has received grant funding from the Washington Global Health Alliance  for the development of a minimally-invasive autopsy for low-resource settings.CLF, JM, and DJR received funding from the INDEPTH Network to attend the 2011 Global Congress on Verbal Autopsy: State of the Science and a post-meeting session focused on research opportunities related to diagnostic pathology autopsies and verbal autopsies in Bali, Indonesia, in February 2011.CLF, JM, and DJR participated in the discussion of the concepts. CLF drafted the manuscript. All authors read, revised, edited, and approved the manuscript.


Gonadotropin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH) neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R), GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG) axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin, and glucocorticoids, to control avian and mammalian reproduction. The neuroendocrine integration of environmental and internal signals controls reproduction across vertebrate species. The reproductive axis of vertebrates integrates information from a wide range of systems via direct and indirect neurochemical inputs. Many of the neuropeptidergic pathways involved in the transduction of environmental stimuli into neuroendocrine signals have been well-studied. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), is the primary factor regulating secretion of both of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and acts as a key neurohormone for vertebrate reproduction. Since the discovery of GnRH in the brain of mammals at the beginning of 1970s    in the hypothalamus and their major projections reach the median eminence of the hypothalamus  with extensive projections to hypothothamic and limbic structures  couples to Gαi to inhibit AC  and is responsible for the temporary cessation of reproductive activities in response to environmental stimuli such as stress . If GnIH is involved in the control of reproductive functions in hamsters, the expressions of GnIH precursor mRNA and GnIH peptides should be regulated by photoperiod and melatonin. We found that expression of GnIH precursor mRNA, GnIH-immunoreactivity in GnIH-ir perikarya and GnIH-ir fiber density decreased under SD photoperiod compared to LD in Siberian hamsters, a highly photoperiodic mammalian species (Ubuka et al., There are different actions of melatonin on GnIH expression across species Figure . MelatonSeveral lines of evidence indicate that kisspeptin and GnIH might work in concert to guide seasonal changes in reproduction across species (reviewed in Simonneaux et al., Calisi et al.  hypothesKirby et al.  also invIn birds, termination of breeding is coincident with long-duration melatonin secretion in the fall. Although the termination of breeding results from refractoriness to melatonin stimulation, given the actions on melatonin on GnIH (Ubuka et al., As in birds, mammals in their natural environments are faced with the challenge of maximizing reproductive success while considering obstacles to survival such as reduced food availability and inclement weather Bronson, . As a reThe discovery of GnIH has fundamentally changed our understanding of hypothalamic control of reproduction. Recent studies on photoperiodic birds and mammals have demonstrated that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Melatonin, a nocturnal hormone, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail and rats. A similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH is found in hamsters and sheep. The variety of melatonin actions and modes of regulation of GnIH raise interesting questions as to the evolution of GnIH and its adaptive significance. Recent studies have further demonstrated that stress induces GnIH expressions in birds and mammals. GnIH may therefore be a mediator of stress-induced reproductive disruption. Thus, the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin, and glucocorticoids, is important for the control of avian and mammalian reproduction.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.