Malaria, Epstein-Barr virus infection and the pathogenesis of Burkitt's lymphoma.

A geographical and causal connection has long been recognized between malaria, Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the underlying mechanisms remain obscure. Potential clues are that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and depends on it for its biological activities; secondly, alterations in vitamin A (retinoid) metabolism have been implicated in many forms of cancer, including BL. The first author has proposed that the merozoite-stage malaria parasite, emerging from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to invade the red blood cells, causing anemia and other signs and symptoms of the disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR, Path Global Health 2013;107(3):122-9). Repeated episodes of malaria would therefore be expected to expose the tissues of affected individuals to potentially toxic doses of vitamin A. It is proposed that such episodes activate latent EBV infection, which in turn activates retinoid-responsive genes. Expression of these genes enhances viral replication and induces germinal center (GC) B cell expansion, activation-induced cytidine deaminase (AID) expression, and c-myc translocation, which in turn predisposes to BL. Thus, an endogenous form of retinoid toxicity related to malaria infection may be the common factor linking frequent malaria, EBV infection and BL, whereby prolonged exposure of lymphatic tissues to high concentrations of retinoids may combine to induce B-cell translocation and increase the risk of Burkitt's lymphoma.

Toward a Theory of Stuttering.

Stuttering affects about 1% of the general population and from 8 to 11% of children. The onset of persistent developmental stuttering (PDS) typically occurs between 2 and 4 years of age. The etiology of stuttering is unknown and a unifying hypothesis is lacking. Clues to the pathogenesis of stuttering include the following observations: PDS is associated with adverse perinatal outcomes and birth-associated trauma; stuttering can recur or develop in adulthood following traumatic events such as brain injury and stroke; PDS is associated with structural and functional abnormalities in the brain associated with speech and language; and stuttering resolves spontaneously in a high percentage of affected children. Evidence marshaled from the literature on stuttering and from related sources suggests the hypothesis that stuttering is a neuro-motor disorder resulting from perinatal or later-onset hypoxic-ischemic injury (HII), and that chronic stuttering and its behavioral correlates are manifestations of recurrent transient ischemic episodes affecting speech-motor pathways. The hypothesis could be tested by comparing children who stutter and nonstutterers (controls) in terms of the occurrence of perinatal trauma, based on birth records, and by determining rates of stuttering in children exposed to HII during the perinatal period. Subject to testing, the hypothesis suggests that interventions to increase brain perfusion directly could be effective both in the treatment of stuttering and its prevention at the time of birth or later trauma.

Identifying Children with Intellectual Disabilities in the Tribal Population of Barwani District in State of Madhya Pradesh, India.

BACKGROUND: Low-and middle-income countries (LAMI) lack an integrated and systematic approach to identify people with intellectual disabilities. Screening surveys are considered resource-intensive; therefore, alternative approaches are needed. This study attempted to identify children up to age 18 years with intellectual disabilities through a mixed-method approach involving focus group interviews (FGIs) and door-to-door surveys. MATERIALS AND METHODS: Focus groups were conducted with the assistance and involvement of local leaders in four villages of Barwani district of Madhya Pradesh with a 99% tribal population in all four villages. A formal survey of the community was then conducted to determine the prevalence of intellectual disabilities based on a standardized screening instrument (NIMH-DDS). RESULTS: Thirty focus group interviews were conducted involving 387 participants (males 284, females 103) over a period of 13 days. The entire adult population (N = 8797) was then surveyed for intellectual disabilities using a standardized screening instrument. The data revealed a close similarity in the prevalence rates of intellectual disabilities, as determined by the two approaches (Focus Group Interviews, 5.22/1000 versus Survey, 5.57/1000). CONCLUSION: A qualitative method using FGIs successfully identified people with intellectual disabilities in an economically deprived tribal area, showing that a community-based approach provides a close estimate of intellectual disabilities based on a formal survey using standard diagnostic criteria. These data suggest that FGI, along with other qualitative data, could be helpful in designing and in serving as an entree for community-based interventions.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role?

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with <10% body surface skin detachment. The syndrome can be induced by numerous medications and typically occurs 1-4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression.

Estimating the unit costs of public hospitals and primary healthcare centers.

BACKGROUND: Many factors have affected the rise of health expenditures, such as high-cost medical technologies, changes in disease patterns and increasing demand for health services. All countries allocate a significant portion of resources to the health sector. In 2008, the gross domestic product of Palestine was estimated to be at $6.108bn (current price) or about $1697 per capita. Health expenditures are estimated at 15.6% of the gross domestic product, almost as much as those of Germany, Japan and other developed countries. The numbers of hospitals, hospital beds and primary healthcare centers in the country have all increased. The Ministry of Health (MOH) currently operates 27 of 76 hospitals, with a total of 3074 beds, which represent 61% of total beds of all hospitals in the Palestinian Authorities area. Also, the MOH is operating 453 of 706 Primary Health Care facilities. By 2007, about 40 000 people were employed in different sectors of the health system, with 33% employed by the MOH. AIM: This purpose of this study was to develop a financing strategy to help cover some or all of the costs involved in operating such institutions and to estimate the unit cost of primary and secondary programs and departments. METHODS: A retrospective study was carried out on data from government hospitals and primary healthcare centers to identify and analyze the costs and output (patient-related services) and to estimate the unit cost of health services provided by hospitals and PHCs during the year 2008. All operating costs are assigned and allocated to the departments at MOH hospitals and primary health care centers (PPHCs) and are identified as overhead departments, intermediate-service and final-service departments. Intermediate-service departments provide procedures and services to patients in the final-service departments. The costs of the overhead departments are distributed to the intermediate-service and final-service departments through a step-down method, according to allocation criteria devised to resemble as closely as possible the actual use of resources by each of the departments. The data were analyzed using spss. Data cleaning was carried out by cross-validating the results through conducting cross-tabulations between the hospital/center and section/program to identify errors from the data collection or entry process. Depreciation of assets and the consumption of capital costs are ignored in this study, as it is difficult to evaluate the MOH facilities owing to a lack of recording of depreciation of assets or other costs of servicing capital assets. RESULTS: Inpatient costs contributed about 75% of all costs, whereas outpatient services contributed the remaining 25% of total costs. The average cost per visit was $13.00 for outpatient departments, whereas the average cost per patient day for inpatient departments was $90.00. As for the unit cost for each department, intensive care unit and intermediate care unit services were the highest among all categories of daily hospital services ($208.00). This is in contrast to surgical operations ($124.00), specialized surgeries ($106.00), delivery department ($99.00), orthopedics ($98.50) and general surgery ($85.00). The lowest unit cost was found in the neonatology department ($72.00). In PHCs, the unit cost per visit was highest for psychiatry programs ($26.00), followed by other programs ($21.50), chronic diseases ($21.00), maternal and child health ($11.50), preventive programs ($9.00) and general medicine ($6.50). The exchange rate listed by The Wall Street Journal as of Wednesday August 25, 2010 is 1 US dollar = 3.82 new Israeli shekel (NIS). CONCLUSION: The findings have implications for policy and decision making in the health sector in Palestine concerning the cost of services provided by hospitals and PHCs. The availability of a standardized data set for cost assessment would greatly enhance and improve the quality of financial information as well as efficiency in the use of scarce resources.

Understanding health disparities affecting people of West Central African descent in the United States: An evolutionary perspective.

Human populations adapting to diverse aspects of their environment such as climate and pathogens leave signatures of genetic variation. This principle may apply to people of West Central African descent in the United States, who are at increased risk of certain chronic conditions and diseases compared to their European counterparts. Less well known is that they are also at reduced risk of other diseases. While discriminatory practices in the United States continue to affect access to and the quality of healthcare, the health disparities affecting African Americans may also be due in part to evolutionary adaptations to the original environment of sub-Saharan Africa, which involved continuous exposure to the vectors of potentially lethal endemic tropical diseases. Evidence is presented that these organisms selectively absorb vitamin A from the host, and its use in parasite reproduction contributes to the signs and symptoms of the respective diseases. These evolutionary adaptations included (1) sequestering vitamin A away from the liver to other organs, to reduce accessibility to the invaders; and (2) reducing the metabolism and catabolism of vitamin A (vA), causing it to accumulate to subtoxic concentrations and weaken the organisms, thereby reducing the risk of severe disease. However, in the environment of North America, lacking vA-absorbing parasites and with a mainly dairy-based diet that is high in vA, this combination of factors is hypothesized to lead to the accumulation of vA and to increased sensitivity to vA as a toxin, which contribute to the health disparities affecting African Americans. vA toxicity is linked to numerous acute and chronic conditions via mitochondrial dysfunction and apoptosis. Subject to testing, the hypothesis suggests that the adoption of traditional or modified West Central African-style diets that are low in vA and high in vA-absorbing fiber hold promise for disease prevention and treatment, and as a population-based strategy for health maintenance and longevity.

Understanding Mass Panic and Other Collective Responses to Threat and Disaster.

While mass panic (and/or violence) and self-preservation are often assumed to be the natural response to physical danger and perceived entrapment, the literature indicates that expressions of mutual aid are common and often predominate, and collective flight may be so delayed that survival is threatened. In fact, the typical response to a variety of threats and disasters is not to flee but to seek the proximity of familiar persons and places; moreover, separation from attachment figures is a greater stressor than physical danger. Such observations can be explained by an alternative "social attachment" model that recognizes the fundamentally gregarious nature of human beings and the primacy of attachments. In the relatively rare instances where flight occurs, the latter can be understood as one aspect of a more general affiliative response that involves escaping from certain situations and moving toward other situations that are perceived as familiar but which may not necessarily be objectively safe. The occurrence of flight-and-affiliation depends mainly on the social context and especially the whereabouts of familiar persons (i.e., attachment figures); their physical presence has a calming effect and reduces the probability of flight-and-affiliation, while their absence has the opposite effect. Combining the factors of perceived physical danger and the location of attachment figures results in a four-fold typology that encompasses a wide spectrum of collective responses to threat and disaster. Implications of the model for predicting community responses to terrorist attacks and/or use of weapons of mass destruction are briefly discussed.

Causes of traumatic brain injury in patients admitted to Rafidia, Al-Ittihad and the specialized Arab hospitals, Palestine, 2006?2007.

PRIMARY OBJECTIVE: The eruption of Al-Aqsa Intifada created a war situation in Palestine, increasing the number of firearms injuries caused by occupying Israeli forces as well as disabling head injuries. No data were available to the Palestinian Ministry of Health and other health organizations on traumatic brain injury (TBI) in Palestine. This study, therefore, sought to determine the causes and outcomes of TBI in patients who were admitted to three hospitals in Nablus, Palestine. RESEARCH DESIGN: Retrospective review of medical records and contacts with patients and/or caregivers. METHODS AND PROCEDURES: The medical records of patients who were diagnosed with TBI (n=312) and admitted to any one of the three hospitals in 2006 and 2007 were reviewed. Data were also obtained from follow-up home visits and telephone calls with consenting patients and/or caregivers. MAIN OUTCOMES AND RESULTS: The major causes of TBI were assault (33%), falls (32.1%), road traffic crashes (29.8%) and impacts from heavy objects (3.2%). Gunshot wounds are a major cause of head injury in Palestine. CONCLUSIONS: The study shows that assault with firearms is the most frequent cause of TBI in this population and that patients with head injuries due to assault have poorer outcomes at discharge than those injured in other ways.

Liver Damage and Exposure to Toxic Concentrations of Endogenous Retinoids in the Pathogenesis of COVID-19 Disease: Hypothesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a marked tropism for the biliary tract; it damages the bile ducts and hepatocytes and can lead to liver decompensation, cirrhosis, and sepsis. The pathogenesis of liver damage and its association with damage to the lung, heart, and brain and to the other protean manifestations of COVID-19 disease are not fully understood. In particular, tissue damage from thinning and leaky blood vessels appears to result from an inflammatory response to the virus rather than the virus itself. This article outlines a new hypothesis of the nature of the inflammatory factor responsible for tissue damage in COVID-19. Review of the literature reveals that COVID-19 disease closely resembles an endogenous form of hypervitaminosis A. We propose that SARS-CoV-2 virus-induced liver damage causes retinoic acid and stored retinyl esters to be released into the circulation in toxic concentrations, unbound to protein, with resulting damage to organs including the lungs, heart, blood vessels, and skin. Several lines of evidence support this model of disease causation. Subject to testing, strategies for the effective treatment and prevention of COVID-19 could include targeting the action and accumulation of retinoids.

Multiple Vaccinations and the Enigma of Vaccine Injury.

A growing number of vaccines are administered at the same time or in close succession, increasing the complexity of assessing vaccine safety. Individual vaccines are assumed to have no other effect than protection against the targeted pathogen, but vaccines also have nonspecific and interactive effects, the outcomes of which can be beneficial or harmful. To date, no controlled trials and very few observational studies have determined the impact of vaccination schedules on overall health. The balance of the risks and benefits from mass vaccination therefore remains uncertain. Recent studies worryingly suggest links between multiple vaccinations and increased risks of diverse multisystem health problems, including allergies, infections, and neuropsychiatric or neurodevelopmental disorders. Here, we propose that, in susceptible persons, multiple vaccinations activate the retinoid cascade and trigger apoptotic hepatitis, leading to cholestatic liver dysfunction, in which stored vitamin A compounds (retinyl esters and retinoic acid) enter the circulation in toxic concentrations; this induces endogenous forms of hypervitaminosis A, with the severity of adverse outcomes being directly proportional to the concentration of circulating retinoids. In very low concentrations, vitamin A and its major metabolite retinoic acid contribute to immune function and to the process of immunization, whereas excess vitamin A increases the risk of adverse events, including common "side-effects" as well as chronic adverse outcomes. The increasing rates of allergy, ear infections, and neurodevelopmental disorders (NDDs) in countries with high rates of vaccination could be related to mass vaccination and to its impact on liver function and vitamin A metabolism, collectively representing endogenous manifestations of hypervitaminosis A. Further studies of health outcomes in vaccinated and unvaccinated groups are urgently needed, to increase understanding of the pathophysiology and treatment of vaccine injury, to identify the risk factors and screen for vaccine injury, to inform public health policy on potential hazards related to vaccination schedules, and to optimize the safety and benefits of vaccines.

On the association between low resting heart rate and chronic aggression: retinoid toxicity hypothesis.

Low resting heart rate is a strong and consistent predictor of conduct disorder and chronic aggression. Explanations such as fearlessness and low arousal-induced stimulus-seeking have been offered, assuming a causal association between the phenomena, but the origin of low heart rate and its significance for understanding aggression and violence remain obscure. Retinoids (vitamin A and its congeners) play important roles in embryogenesis and neural development. Several lines of evidence also suggest a causal role of retinoids in aggression as well as cognitive and mood disorders. The hypothesis is proposed that retinoid overexpression in utero induces, via a noradrenergic-to-cholinergic switch, alterations in cardiac functioning and hemodynamics resulting in low resting heart rate, brain structural and functional changes, minor physical anomalies, and persistent aggression. Retinoid toxicity occurring early in pregnancy could represent a final common pathway by which various prenatal challenges result in conduct disorder and chronic aggression (e.g., maternal cigarette smoking, alcohol consumption, drug use, exposure to environmental chemicals, stress, trauma or infection). Implications of the model for understanding related aspects of chronic aggression are discussed, as well as strategies for prevention and treatment.

Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism.

Symptoms of bone pain and skin rashes are not uncommon following a variety of infectious illnesses, but the underlying mechanisms are not well understood. The case of a 9-year-old boy with autism was recently described, who was hospitalized because of pain in the right hip, refusal to walk, fatigue, irritability, skin rash, and subsequent gingival swelling after an unspecified upper respiratory illness. The boy was diagnosed with scurvy. However, the gingival symptoms occurred after treatment with indomethacin, which lowers vitamin C levels; severe bone pain and fatigue are also well-documented symptoms of hypervitaminosis A. This review of a case report of a boy with autism provides an opportunity to present a new hypothesis of the mechanism of these postinfection symptoms in the context of an increasingly common condition of childhood.

Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism.

Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection occurs early in pregnancy. As many as 8%-13% of children with CRS developed autism during the rubella epidemic of the 1960s compared to the background rate of about 1 new case per 5000 children. Rubella infection and CRS are now rare in the U.S. and in Europe due to widespread vaccination. However, autism rates have risen dramatically in recent decades to about 3% of children today, with many cases appearing after a period of normal development ('regressive autism'). Evidence is reviewed here suggesting that the signs and symptoms of rubella may be due to alterations in the hepatic metabolism of vitamin A (retinoids), precipitated by the acute phase of the infection. The infection causes mild liver dysfunction and the spillage of stored vitamin A compounds into the circulation, resulting in an endogenous form of hypervitaminosis A. Given that vitamin A is a known teratogen, it is suggested that rubella infection occurring in the early weeks of pregnancy causes CRS through maternal liver dysfunction and exposure of the developing fetus to excessive vitamin A. On this view, the multiple manifestations of CRS and associated autism represent endogenous forms of hypervitaminosis A. It is further proposed that regressive autism results primarily from post-natal influences of a liver-damaging nature and exposure to excess vitamin A, inducing CRS-like features as a function of vitamin A toxicity, but without the associated dysmorphogenesis. A number of environmental factors are discussed that may plausibly be candidates for this role, and suggestions are offered for testing the model. The model also suggests a number of measures that may be effective both in reducing the risk of fetal CRS in women who acquire rubella in their first trimester and in reversing or minimizing regressive autism among children in whom the diagnosis is suspected or confirmed.

Gulf War Illness: Unifying Hypothesis for a Continuing Health Problem.

An estimated 25%⁻32% of veterans of the 1991 Gulf War continue to experience multiple unexplained health problems known as Gulf War Illness (GWI). GWI encompasses chronic pain, musculoskeletal weakness, headache, fatigue, cognitive deficits, alterations in mood, and numerous multi-system complaints. Most potential exposures implicated in GWI were not well documented but included varying levels of several neurotoxicants as well as the anticholinergic drug pyridostigmine bromide (PB), which was routinely taken as prophylaxis against the nerve agent soman. While some veterans also took chloroquine as an antimalarial agent, the literature suggests an association between receipt of multiple vaccinations prior to or during the conflict (perhaps combined with other exposures), and GWI. In-theater exposures may account for any single individual veteran's ill health but many veterans of the same era who were not deployed overseas also suffer the same or similar symptoms. The features of GWI also overlap with those of fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity, in all of which liver dysfunction has been documented, suggesting a unifying hypothesis. It is proposed that multiple vaccinations, with concurrent or subsequent exposure to PB or additional chemical insults of a liver-damaging nature, plausibly explain the pathogenesis and the observed chronicity of GWI. The suggested mechanism for GWI is thus a chemically-induced impaired liver function, with the spillage of stored vitamin A compounds ("retinoids") into the circulation in toxic concentrations, resulting in an endogenous chronic form of hypervitaminosis A. Implications of the hypothesis are briefly reviewed.

Confronting the impact of teen pregnancy in Mississippi: the need for after-school programs.

Although rates have decreased 8% since 2014, teen pregnancy remains a substantial public health and social problem in Mississippi and elsewhere in the US. Evidence suggests that, among teenagers, the after-school hours from 3 to 6 pm are peak times of risky sexual activity. This paper reviews recent research and programs concerning sexual risk behavior among adolescents and proposes that after-school programs would increase the daily period of supervised activity and thereby reduce risks not only of pregnancy and sexually transmitted diseases but would also serve to enhance scholastic attainment and hence career prospects for the future. After-school programs from 3 to 6 p.m. should incorporate a multifaceted model that includes academic enhancement and recreational activities as well as curriculum-based sex education, youth development, and service learning.

Disaster mythology and fact: Hurricane Katrina and social attachment.

Misconceptions about disasters and their social and health consequences remain prevalent despite considerable research evidence to the contrary. Eight such myths and their factual counterparts were reviewed in a classic report on the public health impact of disasters by Claude de Ville de Goyet entitled, The Role of WHO in Disaster Management: Relief, Rehabilitation, and Reconstruction (Geneva, World Health Organization, 1991), and two additional myths and facts were added by Pan American Health Organization. In this article, we reconsider these myths and facts in relation to Hurricane Katrina, with particular emphasis on psychosocial needs and behaviors, based on data gleaned from scientific sources as well as printed and electronic media reports. The review suggests that preparedness plans for disasters involving forced mass evacuation and resettlement should place a high priority on keeping families together--and even entire neighborhoods, where possible--so as to preserve the familiar and thereby minimize the adverse effects of separation and major dislocation on mental and physical health.

Using Social Cognitive Theory to Predict Medication Compliance Behavior in Patients with Depression in Southern United States in 2016 in a Cross-Sectional Study.

Introduction: Depression is a major public health issue. One of the concerns in depression research and practice pertains to non-compliance to prescribed medications. The purpose of the study was to predict compliance with medication use for patients with depression using social cognitive theory (SCT). Based on this study it was envisaged that recommendations for interventions to enhance compliance for medication use could be developed for patients with depression. Methods: The study was conducted using cross sectional design (n=148) in southern United States with a convenience sample of clinic-based depression patients with a 37-item valid and reliable questionnaire. Sample size was calculated to be 148 using G*Power (five predictors with a 0.80 power at the 0.05 alpha level and an estimated effect size of 0.10 with an inflation by 10% for missing data). Social cognitive theory constructs of expectations, self-efficacy and self-efficacy in overcoming barriers, self-control, and environment were reified. Data were analyzed using multiple linear regression and multiple logistic regression analyses. Results: Self-control for taking medication for depression (P=0.04), expectations for taking medication for depression (P=0.025), age (P<0.0001) and race (P=0.04) were significantly related to intent for taking medication for depression (Adjusted R2 = 0.183). In race, Blacks had lower intent to take medication for depression. Conclusion: Social cognitive theory is weakly predictive with low explained variance for taking medication for depression. It needs to be bolstered by newer theories like integrative model or multi-theory model of health behavior change for designing educational interventions aimed at enhancing compliance to medication for depression.