Garcinia or more specifically hydroxycitric acid (HCA) extracted from Garcinia has been widely used. The evaluation of the potential toxicity of weight control supplement is of the utmost importance as it requires long term continuous consumption in order to maintain its effects. Majority of reports demonstrated the efficacy of Garcinia/HCA without any toxicity found. However, a few clinical toxicity reports on weight-loss diet supplements of which some were combinations that included Garcinia/HCA as an active ingredient showed potential toxicity towards spermatogenesis. Nonetheless, it cannot be concluded that Garcinia/HCA is unsafe. Those products which have been reported to possess adverse effects are either polyherbal or multi-component in nature. To date, there is no case study or report showing the direct adverse effect of HCA. The structure, mechanism of action, long history of the use of Garcinia/HCA and comprehensive scientific evidence had shown “no observed adverse effect level (NOAEL)” at levels up to 2800 mg/day, suggesting its safety for use.Obesity is one of the pandemic chronic diseases commonly associated with health disorders such as heart attack, high blood pressure, diabetes or even cancer. Among the current natural products for obesity and weight control,  Focus on disease prevention by complementary supplementation of nutraceutical products to medication has heralded the growing demand for healthy food. In addition, rising healthcare costs have greatly boosted the growth of the nutraceutical industry . NonetheGarcinia has been used for centuries in Asian countries for culinary purposes as a condiment and flavoring agent in place of tamarind or lemon, and to make meals more filling. Garcinia or more specifically G. cambogia, G. atroviridis, and G. indica have been found to contain large amounts of hydroxycitric acid (HCA) [Garcinia/HCA exerting antiobesity effects, the results on the effects of HCA on appetite, body weight and energy expenditure (EE), and its potential contribution as a weight loss agent in humans were controversial [in vitro, in vivo, and clinical trials on the safety of Garcinia/HCA as a dietary supplement for treating obesity.id (HCA) . It has id (HCA) , 9. Previd (HCA) . Furtherid (HCA) , 12. It id (HCA)  and humaid (HCA) , as wellid (HCA) . Despiteoversial –19. Althoversial  did not in vitro antiproliferative effects of the aqueous extracts of dried fruit rind of G. indica  on Balb/c 3T3 mouse fibroblasts and human peripheral lymphocytes. The results showed that G. indica extracts inhibited lymphocytes and 3T3 fibroblast cell survival. Thus, the authors concluded that G. indica extracts exhibited pronounced cytotoxic effects. However, there was a flaw in their methodology, since the authors also reported that Azadirachta indica and Coleus aromaticus exhibited cytotoxic effects on lymphocytes despite the low cell viability in the control group (only 50–55% of viable lymphocytes). In the case of G. indica, percentage of viability in lymphocytes was not even mentioned. Thus, definitive conclusion of G. indica induced cytotoxicity could not be drawn due to the poorly-described methodology of their study.Varalakshmi et al.  evaluatein vitro chromosomal aberration (CA) test, and in vivo micronucleus (MN) test. For the Ames test (plate incorporation method), five Salmonella typhimurium strains  were used and six different doses of HCA-SX  were tested. No significant increase (P < 0.05) in the number of revertants was observed, indicating that HCA-SX did not induce mutagenic activity in any of the five bacterial strains tested, under any of the activation conditions examined. In the CA test, HCA-SX-treated Chinese hamster ovary cells were fixed on glass slides and stained with Giemsa staining solution. The stained cells were viewed under an optical microscope, where at least 100 metaphases were counted at a resolution of 1000x. No significant mutagenic potency was detected by the CA tests. In the MN test, suspensions containing HCA-SX were administered to 7-to-8-week-old old ICR mice via intraperitoneal (ip) injection as follows: group 1, negative control ; group 2, positive control ; groups 3, 4, 5, 6, and 7, HCA-SX-treated . The bone marrow cells were fixed, stained, and viewed using an optical microscope. HCA tended to increase the number of micronucleated polychromatic erythrocytes (MNPCEs/1000 polychromatic erythrocytes) and the polychromatic erythrocytes/normochromatic erythrocytes PCE/(PCE + NCE) ratios, and they reached significance level at a dose of 12,500 μmol/kg. Taken all together, the authors suggested that HCA-SX possessed no genotoxic effect by bacterial or by chromosome aberration testing, but preferentially induced micronuclei.K. H. H. HHLee and B. M. Lee  conducteμmol/kg) may have been too high and exceeded the maximum tolerated dose. Besides, Lau and colleagues pointed out several limitations in the experimental design and the interpretation of the results, as follows: (1) selection of ip delivery of HCA-SX rather than the recommended oral administration for this supplement, (2) selection of DMSO as a vehicle, which was not recommended for the in vivo rodent erythrocyte micronucleus assay, (3) five different HCA-SX doses were selected in the absence of a prior ip LD50 determination, (4) the range of doses (increased by a factor of 5) chosen in the study deviated from that of the conventional dose levels used in toxicological studies, (5) no significant difference (P < 0.05) in the values of percent MNPCE between 500 μmol/kg and 12,500 μmol/kg, suggesting the use of the highest dose was probably unnecessary, and (7) poor statistical analysis.However, Lau et al.  refuted 50) was determined to evaluate the potential systemic toxicity of HCA-SX when administered as a single dose to male and female Albino rats. HCA-SX at a single dose of 5000 mg/kg was administered orally via gastric intubation in a dose volume of 10 mL/kg. Toxicological studies revealed no death, remarkable body weight changes or gross necropsy findings in Albino rats following a single oral dose of 5000 mg/kg, equivalent to 350 g or 233 times the maximum dose of 1.5 g/day of HCA in humans. Clinical findings were limited to soft stool and rales for one male and two female rats, respectively. Taken all together, the authors suggested that the oral LD50 of HCA-SX in rats  was more than 5000 mg/kg [Acute safety studies of HCA-SX (containing 60% HCA) as demonstrated in acute oral and dermal toxicity studies were conducted , 12. In P < 0.05) reduced body weight and feed intake in both male and female rats, but not water intake and lipid peroxidation. Moreover, no significant effects on liver and testis weight, hepatic and testicular DNA fragmentation morphology were observed in HCA-SX treated rats [However, a long-term study on the safety and efficacy of HCA-SX or any of the HCA products still remained to be conducted. Hence, Shara et al. , 25 exteted rats .Mycoplasma sp. The minimal hepatocyte vacuolation noted in HCA-SX groups were limited and not considered significant/treatment-related as one control animal had a similar lesion. Another change noted was within the glandular stomach where the mucosa of the glandular stomach of one animal was severely atrophied and mineralized. Besides, scattered minimal or mild foci of gastric gland dilation were also noted. No necrosis or inflammation was seen. These changes were noted in animals supplemented with HCA-SX as well as the untreated control group. The results obtained did not indicate the change being either more severe or more numerous in any particular dose group. In any case, the morphologically changes noted appeared to be minimal and not significant, thus indicating the safety and efficacy of HCA-SX in weight management [Further evaluation on the safety of HCA-SX was conducted by Shara et al.  where vinagement .Another study performed by Roy et al.  showed tIn another study, the potential systemic toxicity and local irritative potential of HCA-SX were evaluated using Albino rabbits. HCA-SX administration at a single dose of 500 mg/site was directly applied to shaved intact skin to assess the local dermal irritative potential. Each animal received a single, 4 h semioccluded exposure and application sites were evaluated at approximately 30–60 min and 24, 48, and 72 h after patch removal. Minimal irritation was noted in this study. Very slight erythema on a single animal was noted at the beginning of observation, but completely subsided by the end of day 1. All dose sites were stained yellow. No gross toxicological pathology  was found on autopsy. HCA-SX was classified as nonirritating, as the primary irritation index was calculated to be 0 .P < 0.05) was noted. Occular observation revealed that a small area of inflammatory exudate with enlarged blood vessels was present at the apex of the lower conjunctival sac for three rabbits on day 7. The inflammation completely subsided by the end of study for two animals, but not the other one. Positive iridal and conjunctival reactions were induced in all animals, but subsided within 48 h. The maximum average score of 15 (out of 110) was obtained, indicating HCA-SX possessed mild irritation on eye [HCA-SX was administrated by direct conjunctival instillation, a standard administration route for local ocular irritative potential assessment. HCA-SX at a dose of 54 mg/right eye was applied directly into the cupped lower conjunctival sac of the right (test) eye of six New Zealand white Albino rabbits. In this study, no death or significant changes in body weights -HCA, the ratio of free to lactone form was 36.6 to 63.4) in suppression of body fat accumulation and the safety of its high doses. Diets containing different levels of G. cambogia  were fed to 6-week-old male Zucker obese rats for 92 or 93 days. Significant increases (P < 0.05) in ATP-citrate lyase activity and concentrations of liver glycogen, and reduction (P < 0.05) in plasma nonesterified fatty acid were detected in rats fed with 154 mmol HCA/kg diet. A dietary HCA level over 3.0 wt% (154 mmol HCA/kg diet) caused severe diarrhea in rat models. HCA administration reduced the testis weights by half in male Zucker obese rats. Histopathological examinations revealed marked testicular atrophy and impairment of spermatogenesis in the highest and second highest HCA groups. However, no significant differences in all the parameters in this study were observed in rats fed with 0, 10, and 51 mmol HCA/kg diet. Taken all together, the authors suggested that high dose of G. cambogia effectively suppresses fat accumulation in developing male Zucker obese rats, but was highly toxic to the testis.o et al.  investigG. cambogia powder (containing 41.2 wt% of (−)-HCA, the ratio of free to lactone form was 36.6 to 63.4) at 102 mmol/kg diet in young Fischer 344 male rats. By considering that 4,4-dimethyl-5α-cholesta-8,24-diene-3β-ol, a testis meiosis-activating sterole (T-MAS), was a specific intermediate product of cholesterol biosynthesis in testicular germ cells, the authors elucidated the relationship between impaired spermatogenesis and MAS production in rats testis, postingestion of G. cambogia. Histopathology examinations of rat testis showed that spermatogenesis was immature in all rats of both treatment and control group after 2 weeks of G. cambogia administration . After 4 weeks , normal spermatogenesis was observed in control group, with abundance of elongation and elongated spermatids in all seminiferous tubules. On the contrary, there was a complete absence of spermatid elongation in the G. cambogia group, with some round spermatids being released in clusters instead. The concentrations of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-B, the four hormones related to spermatogenesis, were measured. No significant difference (P < 0.05) in testosterone and LH concentrations were detected between groups. However, a significant reduction of inhibin-B concentration was detected in the G. cambogia-treated group, concurrently with an increase in FSH concentration, compared to the control group after 2 weeks of feeding. Similar results were obtained after 4 weeks of feeding, when the rats reached sexual maturation. Inhibin-B is an important marker of the function of Sertoli cells and spermatogenesis. The concomitant decrease in inhibin-B and increase in FSH concentrations indicated impaired spermatogenesis [G. cambogia, probably associated with a blockade of MAS substances accumulation.In a continuation to the study conducted by Saito et al. , Kiyose ogenesis –30. TherWith regards to the study conducted by Saito et al. , BurdockG. cambogia/HCA has been used by women for weight loss after delivery. However, Shara et al. [Nevertheless, it would be more convincing to evaluate the effect of HCA consumption in fertility of both male and female models rather than only the testicular function to justify the effect of HCA on reproductive capacity. Pragmatic maternal observations indicated that maternal toxicity might occur due to reduced weight gain during pregnancy. Decrease in body weight of about 20% had been reported to possess adverse effects on fertility and reproduction in rats and mice . In thisa et al. , 25 repoa et al. , 34, 35.0 and F1 generations. These results suggested that the “no observed adverse effect level (NOAEL)” of HCA-SX in both parental and offspring exceeded 10,000 ppm  [A two-generation reproduction toxicity study was also conducted to evaluate the effects of HCA-SX on the reproductive systems of male and female rats, postnatal maturation and reproductive capacity of their offsprings, and possible cumulative effects through multiple generations. Rats were fed with diet containing 0, 1000, 3000, or 10,000 ppm of HCA-SX for a period of 10 weeks prior to mating, during mating, and across two generations, until their termination. No treatment-related adverse effects on reproductive performance in terms of fertility and mating, gestation, parturition, litter properties, lactation, sexual maturity, and development of offspring were observed during HCA-SX exposure of male and female rats from F, resp.) .2 litter of the F1 generation from the two-generation reproductive toxicity study and allowed to grow up to 10 to 12 weeks of age before mating. Dietary exposure levels of 1000, 3000, and 10,000 ppm  were subjected indirectly to the male and female rats in HCA-SX treatment groups during lactation, and directly postweaning (4 weeks old) till they were terminated . Maternal toxicity and effects on the developing embryo were evaluated throughout the gestation period until the 20th day of gestation. Apart from a slight (13%) lowering of maternal body weight gain in the group administered 10,000 ppm HCA-SX, no evidence of maternal toxicity, adverse effects on the parameters evaluated for the gravid uteri, external abnormalities in the fetuses, soft tissue abnormalities in the fetuses, or skeletal abnormalities in the fetuses was noted. The results suggested that HCA-SX (up to dose level of 1240 mg/kg/day) was not teratogenic to Sprague-Dawley rats. Considering the comprehensive reproductive and developmental studies reported on safety profile of HCA [Several mechanism of action studies showed that HCA did not affect fatty acid synthesis in the fetus –39. Jonee of HCA , 36–40, G. cambogia extract ” at levels up to 2800 mg/day, suggesting its safety in-use , 42. In  extract . There aG. cambogia extract/HCA-containing dietary supplement does not justify definitive attribution of causality in most cases. It is impossible to tell with certainty which ingredient(s) is responsible for the adverse effects reported in the various case reports. The majority of the case reports were insufficiently documented to make an informed judgment about a relationship between the use of G. cambogia extract/HCA or G. cambogia extract/HCA-containing dietary supplements and the adverse event in question. Mozersky et al. [G. cambogia extract in clinical trials ranging from 1,500 to 4,667 mg/day (25 to 78 mg/kg/day), whereby their equivalent HCA dose ranging from 900 to 2,800 mg/day (15 to 47 mg/kg/day) is safe for human consumption [G. cambogia is available in capsule or tablet form with a maximum dose of 1,500 mg/day. A study conducted by Deshmukh et al. [A number of hepatotoxicity cases associated with the consumption of hydroxycut had lead to the assumption that HCA is the primary causative agents to the hepatotoxicity –65. Thosy et al.  also sugsumption , 69. G. h et al.  determinG. cambogia extract/HCA as dietary supplements for treating obesity has been established [G. cambogia extract/HCA [G. cambogia/HCA is generally safe and is classified as NOAEL up to 1240 mg/kg/day [G. cambogia extract has been widely used as an antiobesity herbal supplement for decades around the world without a birth defect or reproductive problem suggests that HCA is unlikely to cause reproductive or developmental toxicity. However, most randomized control trials (RCTs) have been conducted on small samples and mainly over a short term. None of them have shown whether the efficacy and safety of G. cambogia extract/HCA consumption persist beyond 12 weeks of intervention. Thus, more long term clinical trials or followups could be conducted, especially on consumers who have been taking HCA for a long period of time to add value to the NOAEL for long-term consumption.Based on the results obtained in an array of toxicological and safety studies, a comprehensive safety profile on ablished , 66, 70 ablished , genotoxablished , 23, acuablished , 12, subablished , 24, 25,ablished –40, and ract/HCA –58 suppo


Maternal near misses are increasingly used to study quality of obstetric care. Inclusion criteria for the identification of near misses are diverse and studies not comparable. WHO developed universal near miss inclusion criteria in 2009 and these criteria have been validated in Brazil and Canada.To validate and refine the WHO near miss criteria in a low-resource setting.A prospective cross-sectional study was performed in a rural referral hospital in Tanzania. From November 2009 until November 2011, all cases of maternal death (MD) and maternal near miss (MNM) were included. For identification of MNM, a local modification of the WHO near miss criteria was used, because most laboratory-based and some management-based criteria could not be applied in this setting. Disease-based criteria were added as they reflect severe maternal morbidity. In the absence of a gold standard for identification of MNM, the clinical WHO criteria were validated for identification of MD.32 MD and 216 MNM were identified using the locally adapted near miss criteria; case fatality rate (CFR) was 12.9%. WHO near miss criteria identified only 60 MNM (CFR 35.6%). All clinical criteria, 25% of the laboratory-based criteria and 50% of the management-based criteria could be applied. The threshold of five units of blood for identification of MNM led to underreporting of MNM. Clinical criteria showed specificity of 99.5% (95%CI: 99.4%–99.7%) and sensitivity of 100% (95%CI: 91.1%–100%). Some inclusion criteria did not contribute to the identification of cases and therefore may be eligible for removal.The applicability of the WHO near miss criteria depends on the local context, e.g. level of health care. The clinical criteria showed good validity. Lowering the threshold for blood transfusion from five to two units in settings without blood bank and addition of disease-based criteria in low-resource settings is recommended. In 2011, 273,465  women died worldwide during pregnancy, childbirth or within 42 days after childbirth Worldwide the numbers of maternal deaths are high, but at hospital level numbers become scarce. It is important to understand the process of care that the patient has undergone in order to improve the quality of care. In this context, near miss events of women who almost died, but survived pregnancy related complications, are increasingly used in order to evaluate the functioning of the health system Identification criteria for maternal near misses or severe acute maternal morbidity were mainly divided into three areas: disease-based, management-based and organ-dysfunction-based criteria The WHO laboratory-based and management-based criteria were validated in Brazil and Canada The aims of this study were 1) to validate the WHO near miss criteria, especially the clinical criteria, in a low-resource setting, and 2) to further refine the WHO near miss criteria. This article reports on the experience of applying the WHO near miss criteria prospectively in a low-resource setting where the burden of maternal mortality and morbidity is high.A prospective cross-sectional study was conducted from November 2009 until November 2011 at Haydom Lutheran Hospital (HLH), a 400-bed referral hospital in Northern Tanzania. The hospital is located in an isolated, rural area, 300 km southwest from the nearest city, Arusha. Extrapolating from the 2002 census, the immediate catchment area covered a population of 327,000 in 2010. The greater reference area covered a population of approximately 2,200,000 All maternal deaths and maternal near misses that were admitted to HLH were prospectively included in the study during the above-mentioned period. In this study, a maternal death (MD) is defined as the death of a woman while pregnant or within 42 days of termination of pregnancy, from any cause. For the identification of maternal near misses, we intended to use the WHO near miss criteria, but not all WHO criteria were applicable in this low-resource setting. Therefore, a local modification of the criteria for use in Haydom was made . The defCases were identified on a daily basis by either the first author (EN) or by one of the two trained research assistants (nurse-midwives). This was achieved through daily participation in the morning report and daily visits to the maternity ward, ICU and the internal medicine ward. When the inclusion criteria were met, a structured questionnaire was filled out after discharge or death of the woman. Data were obtained from hospital files. The completed questionnaires were checked by a second person on missing data or discrepancies. If needed, a copy of the hospital file was checked to validate the recordings. Variables that were collected for this study were information on presence of an inclusion criterion and final outcome (MNM or MD). Furthermore, measurements to identify clinical and laboratory-based criteria were noted . All data were double entered and cross-checked in Epidata Previous validation of the WHO near miss criteria was done with the Sequential Organ Failure Assessment (SOFA) score as gold standard for the definition of MNM In order to refine the WHO near miss criteria, and thereby improve the applicability in practice, we performed a stepwise elimination process, to determine which criteria were most important. The inclusion criteria were ranked from most to least frequently used. Subsequently, the most frequently used inclusion criterion was excluded, and all cases with this inclusion criterion were (temporarily) removed from the database. Thereafter, frequencies of inclusion criteria were calculated again for the remaining cases and a new ranking was created. This stepwise elimination process helped us to rank the inclusion criteria according to importance (frequency of use).Data analysis consisted of frequencies of the use of inclusion criteria, the presence of physical examination and measurement of vital signs, urinary output, oxygen saturation and full blood count. Validity of the  WHO near miss criteria and Haydom near miss criteria was assessed by calculating sensitivity, specificity, positive predictive value and negative predictive value against outcome , among all women who delivered during the study period. All results are reported as number (n) and frequency (%). Analysis was performed using SPSS Statistics, version 20 .The study was performed in full accordance with the guidelines for medical research of the Helsinki declaration of 1975, as revised in 2008. Ethical approval was obtained from the Tanzanian National Institute for Medical Research (NIMR) (reference NIMR/HQ/R.8a/Vol.IX/1247), the Tanzania Commission for Science and Technology (COSTECH) (reference 2012-56-NA-2011-201), and from the VU university medical centre (VUmc), the Netherlands (reference 2011/389). As stated by the VU university medical centre, the study does not fall within the scope of the Medical Research Involving Human Subjects Act, and formal approval was not needed. Data were collected and extracted from patient records without any identification of the subject. Questionnaires were filled in after discharge or death and therefore study inclusion did not have effect on the treatment. Considering this approach and the statement of the VUmc, individually obtained informed consent was not required.According to the local Haydom near miss criteria, 248 women with life-threatening conditions were included in the two-year study period: 216 MNM and 32 MD. When the WHO near miss criteria were applied to this dataset, 92 women with life-threatening conditions remained, of which 60 MNM and 32 MD . In the The difference in the number of near misses can be attributed largely to the different threshold for the transfusion of blood. For the Haydom criteria one unit was chosen, as compared to five units for the WHO criteria. Of 248 women that were included with the Haydom near miss criteria, 184 women received one unit of blood or more, compared to 58 of the 92 women selected with the WHO criteria. Two of the 58 cases had transfusion of five units or more. Other differences in the number of near misses could be attributed to the inclusion of all cases with eclampsia, sepsis, uterine rupture and admission to ICU . Women wMeasurements to identify clinical and laboratory-based criteria were insufficient: 91.5% (n = 227) of 248 women with life-threatening conditions had physical examination on arrival. Blood pressure was measured in 74% (n = 183); pulse rate was noted in 68% (n = 169) and temperature in 65% (n = 161). Urinary output was measured in 10% (n = 25) of all cases. Oxygen saturation on admission was only noted in 4.8% (n = 10) of all women with life-threatening conditions. Full blood count (including platelet count) was taken in 90.1% (n = 155) of 172 women that were ill on arrival.The clinical WHO near miss criteria were validated for identifying maternal deaths . SensitiWhen this stepwise elimination process was repeated for the Haydom near miss criteria, the most frequently used inclusion criteria were: use of blood products (n = 184), admission to ICU (n = 41), sepsis (n = 7), eclampsia (n = 6), and uterine rupture (n = 5). The following criteria were not used: CPR, oxygen saturation <90% for ≥60 min, loss of consciousness lasting >12 h, gasping, intubation and ventilation for ≥60 min not related to anaesthesia, acute thrombocytopenia, respiratory rate >40 or <6/min, stroke, jaundice in the presence of pre-eclampsia, failure to form clots, uncontrollable fit and acute cyanosis.In this paper we report on the applicability and validation of the WHO near miss criteria in a 2-year prospective cross-sectional study in the low-resource setting of a rural referral hospital in Tanzania.The results show that all clinical criteria could be used in this setting. Experience at HLH, however, indicates that it is not easy to recognise clinical criteria. In maternity ward ten nurse-midwives are available each day, divided over three shifts, to take care of 60 in-patients and an average of 15 deliveries per day. Nurse-midwives are the sentinel persons that should identify clinical signs of deterioration of a patient. With this shortage of health care personnel, clinical signs of deterioration may go unnoticed and this could lead to underreporting of maternal near misses.Only 25% of all laboratory-based criteria could be used in HLH. Oxygen saturation measurement in our setting is only available in the ICU, and thus has only been measured in 4.8% of all cases. Although the laboratory-based criteria could be used in settings in Brazil The three management-based criteria that could be used at Haydom were easy to identify and therefore used as an inclusion criterion. Because HLH does not have a well-stocked blood bank, the transfusion of five or more units of blood was considered very unlikely and occurred in only two cases. One woman received one unit of allogeneic blood and five units of auto-transfusion, following ruptured ectopic pregnancy. The other woman was diagnosed with molar pregnancy and received two units of blood in another hospital, before being referred to HLH where she received another three units of blood. Few studies used the WHO near miss criteria for retrospective identification of near misses In our study several inclusion criteria were detected, which did not identify near miss cases independently. These criteria are eligible for removal from the WHO near miss criteria. This will refine the WHO near miss approach and improve its applicability. This is in concordance with Morse et al., who found that only 12 out of 25 WHO near miss criteria contributed to the identification of near misses All studies showed that the applicability of the WHO near miss criteria depends on the local context and the local availability of resources, e.g. level of health care. Therefore we suggest different criteria that account for different levels of health care. For example, in a district hospital in a low-resource setting, sophisticated laboratory-based criteria are better not used. Even then local adaptation might be needed, as in our setting an advanced laboratory allowed platelet count, which is not necessary the case in other district hospitals.Most studies in low-resource settings used disease-based criteria, like eclampsia, sepsis and uterine rupture, to identify near miss cases. Excluding these cases leads to underestimation of maternal near miss cases and therefore we recommend these criteria to be added to the WHO near miss approach, despite the fact that definitions of disease-based criteria may vary among settings.A limitation of our study is that data collection was only done in wards where pregnant women were mostly admitted. It might be possible that we missed cases that were admitted to other wards. However, HLH policy is that all pregnant women are admitted to maternity ward, and therefore the number of cases that might have been missed will be negligible.Poor documentation has negative impact on the identification of inclusion criteria. Human resource shortage and low educational levels of staff may affect the quality of documentation and therefore may negatively interfere with case identification and data collection.We realize that our study is a hospital-based study. Many women who suffer from severe maternal morbidity in the district do not reach the hospital.To our knowledge, this is the first study in which the WHO near miss criteria were used and validated prospectively in a rural referral hospital in a low-resource setting.The applicability of the WHO near miss criteria depends on the local context. In our setting, clinical criteria could be applied and show good sensitivity and specificity. However, sophisticated laboratory and some management-based criteria could not be used. We would recommend lowering the threshold for blood transfusion from five to two units in settings where there is no blood bank. Furthermore, in low-resource settings disease-based criteria should be added to the WHO near miss criteria as they reflect severe maternal morbidity.Future research should focus on validation of the WHO near miss criteria across multiple low-income countries


To account for the widespread human tendency to cooperate in one-shot social dilemmas, some theorists have proposed that cooperators can be reliably detected based on ethological displays that are difficult to fake. Experimental findings have supported the view that cooperators can be distinguished from defectors based on “thin slices” of behavior, but the relevant cues have remained elusive, and the role of the judge's perspective remains unclear. In this study, we followed triadic conversations among unacquainted same-sex college students with unannounced dyadic one-shot prisoner's dilemmas, and asked participants to guess the PD decisions made toward them and among the other two participants. Two other sets of participants guessed the PD decisions after viewing videotape of the conversations, either with foreknowledge (informed), or without foreknowledge (naïve), of the post-conversation PD. Only naïve video viewers approached better-than-chance prediction accuracy, and they were significantly accurate at predicting the PD decisions of only opposite-sexed conversation participants. Four ethological displays recently proposed to cue defection in one-shot social dilemmas  failed to predict either actual defection or guesses of defection by any category of observer. Our results cast doubt on the role of “greenbeard” signals in the evolution of human prosociality, although they suggest that eavesdropping may be more informative about others' cooperative propensities than direct interaction. Humans frequently cooperate with each other in one-shot anonymous economic games Two competing explanations are cultural group selection e.g. , and theDespite these theoretical problems, a growing body of research seems to support the Frank-Hirshleifer model in showing that people can judge others' propensity to defect in one-shot social dilemmas based on brief social interactions. Frank et al. Various sources of information may be reliably indexing future behavior in these studies Particular gestures and postures may also reliably signal cooperative propensities. DeSteno et al. The “thin slice” literature further suggests that immediately observable features of individuals may index cooperative dispositions. Research shows that “thin slices” of behavior can facilitate accurate judgments of stable individual propensities to cooperate dyad-specific probabilities of cooperation, as well as the commonly studied individual-level and contextual variables Most research in this area has been limited to individual-level attributes as cues to defection or exploitation. DeSteno et al. Defector detection may be thus facilitated by many sources of information both about stable behavioral dispositions and context-specific intentions. In addition, in naturalistic settings, the circumstances under which people assess each other's cooperative propensities are quite varied. This implies that a wide range of experimental designs is needed to illuminate the role of defector-detection in supporting the evolution of one-shot cooperation. For example, there is probably considerable variation in the extent to which defector detection is a salient goal while potential judges are processing information relevant to predicting future behavior. In most experimental defector-detection research, participants are informed about the nature of the judgment task they will complete, prior to the presentation of the stimuli  or third party (observer), and whether the judge is present for the face-to-face interaction or sees a videotaped version of it. “Thin slice” research typically privileges experimental control over ecological validity by presenting participants with media-based stimuli nd party face-to-face predictions relative to those of a 3rd party.At least three considerations suggest that patterns of prediction will differ between face-to-face and media-viewing contexts. First, it may be that only face-to-face interactions activate the neurophysiological and hormonal mechanisms underpinning cooperation or trust nd party). Second, the conversation participants guessed their two co-participants' decisions toward each other (3rd party insider). Third, a separate set of participants guessed the conversation participants' PD decisions after viewing a video of the conversation, without being told about the PD before viewing the video (naïve 3rd party outsiders). Finally, another set of participants were told about the PD decision-guessing task before viewing conversation video (informed 3rd party outsiders).In the present study, we address these methodological issues by investigating how two experimental tools frequently used in the study of defector-detection—video-mediation for third party judges, and prior knowledge of an upcoming game—may affect the behavioral predictions that judges make about participant game play in a one-shot PD. We do this by forming conversational triads and comparing the predictions by four types of judges: First, the conversation participants (who had not been told about the PD before beginning the conversation) guessed their two co-participants' decisions toward themselves  were recruited on a USA college campus This study involved three distinct groups of participants. Conversation participants  and informed third party outsiders  were recruited from the same participant pool, during academic years following the completion of the conversation/PD trials. Naïve video viewers received course credit and a $6 payment, and could earn an additional $6 by making accurate predictions about gameplay (see below). Informed video viewers received course credit and a $3 payment, and could earn an additional $12 by making accurate predictions about gameplay. Third party participants were not asked their ages.Naïve third party outsiders . Written informed consent was obtained from all participants in accordance with the terms of these approvals.Conversation participants were informed that their conversation would be videotaped. Logistical and resource constraints limited the protocol to a single video camera, which directly faced one of the three participants. The identity of this participant was determined randomly. From the point of view of video viewers, the other two conversation participants were in profile. After 10 minutes of conversation, participants played an unannounced, computer-moderated one-shot PD toward each of the others. During the PD, they could “Keep” for themselves ( = defect) or “Transfer” to a recipient ( = cooperate) a $3 endowment provided by the experimenter; transferred funds were doubled and added to recipient payoffs. Unilateral defection yielded $9, mutual cooperation yielded $6, mutual defection yielded $3, and unilateral cooperation yielded $0. Participants then guessed how each co-participant played toward them (second party predictions) and toward one another (third party insider predictions). Each correct guess earned them $1. Prior to game play, we informed participants that one of them would not receive their earned payoff, but instead a randomly chosen, realistic payoff. This protected the confidentiality of participants' PD choices without eliminating their relevance to payoffs see . After tarms crossed, lean back, hand touch, and face touch. To ensure comparability, we obtained a detailed coding protocol from D. DeSteno . A second research assistant, also ignorant of our hypotheses, independently coded 6 randomly chosen conversations of the 35 (i.e. 18 of 105 participants) for these four behaviors.Coding of interruptions is described elsewhere JHM prepared video and still photographs for presentation to the naïve and informed video viewers, using SuperLab 4.0. Each naïve video viewer viewed one 10-minute conversation video. Video viewers first acknowledged they had never met the participants in the video. Prior to their viewing, we told naïve video viewers that the video would show a “conversation among three people meeting for the first time. After viewing the tape, you will be asked some questions about the behavior of these people.” After showing the video, we presented the PD instructions to the video viewer, who was asked to guess participant PD decisions (“Keep” or “Transfer”) in each direction for each dyad of conversation participants. This yielded six PD guesses per viewer. Each viewer watched only one conversation video, and each video received a total of two viewer ratings. The procedure was identical for the informed video viewers, except that, before showing them the video, we showed them the PD instructions and explained that they would be asked to guess game play following the video viewing. Informed viewers repeated this for a second video; naïve viewers moved on to rate 21 conversational participants for facial attractiveness on a six-point Likert scale. (They did not rate participants from the video they watched). Both naïve and informed video viewers, like conversation participants, were awarded $1 USD for each correct guess of a PD decision. See arms crossed, lean back, hand touch, and face touch) as an independent variable hypothesized to be inversely associated with probability of cooperating.See We examined frequencies of agreement among guessers, and guesser prediction accuracy, with respect to their deviations from chance frequencies based on the base rates of actual cooperation and predictions of cooperation see . Since eP-values. For all analyses involving PD decisions, cooperation was coded as 1, and defection as 0. All tests are 2-tailed. The data for this study can be accessed in the Dryad repository In relating our independent and dependent variables, we used bivariate and multivariate logistic regression models. Since each actor made multiple and therefore non-independent predictions, we calculated robust standard errors of the odds ratios, clustering by the identity of the individual making the predictions, before calculating confidence intervals and We obtained adequate inter-rater reliabilities of (1) the coding of interruptions between JHM and a research assistant, and (2) facial attractiveness ratings among participant raters (naïve video viewers) lean back behavior could not be reliably coded. These 15 individuals were excluded from analyses of the gestures/postures.Coders were unable to reliably code frequencies of at least one of the 4 gestural/postural behaviors for 15 of the 105 (14.3%) conversation participants. Such cases included, for example, 11 individuals seated in the chair directly facing the camera whose Other missing data points included two conversation participants who declined to play the PD, one conversation participant who declined to guess her co-participants' PD decisions, and 4 naïve video viewers and one informed video viewer each who declined to guess one PD decision. Missing data points were excluded from analyses on a casewise basis.recipient's guesses of actor's decisions toward herself (2nd party); other's guesses of actor's decisions toward recipient (3rd party insider); naïve video viewer (3rd party outsider) guesses; and informed video viewer (3rd party outsider) guesses. Two-sample tests of proportions revealed that unlike conversation participants, video viewers (both naïve and informed) significantly underestimated the actual base rate of cooperation. Third party insiders, compared to all three other types of guessers, expected a significantly higher rate of cooperation that was not significantly different from the actual base rate.In Gervais et al. nd vs. 3rd party insiders; two naïve video viewers; two informed video viewers) agreed at above chance levels . Furthermore, for all PD decisions (N = 204) guessed at by all six participants, we calculated the observed aggregate frequencies (0–6) of guesses of cooperation, and compared these with the frequencies expected by chance based on the observed base rates of cooperation predictions made by the four categories of guessers. If guessers tended to agree, we would expect an overrepresentation of high (5–6) and low (0–1) counts. In fact, the observed counts of 6, 5, 4, 3, 2, 1 and 0 cooperation guesses  were not significantly different from the expected counts of 6.1, 29.3, 58.4, 61.5, 36.1, 11.2 and 1.4 .The six participants who guessed each PD decision did not agree with each other above chance levels. None of the three pairs of guessers (2nd party (recipient guessing actor's PD decision toward himself); 3rd party insider (other guessing actor's PD decision toward recipient); (3) naïve video viewer and (4) informed video viewer. Only naïve video viewers approached significant accuracy. Although we did not predict any sex effects on video viewers' prediction accuracy, post-hoc examination of our data revealed that this trend toward accurate prediction was driven entirely by the guesses of the 29 naïve video viewers who predicted the PD play of conversation participants of the opposite sex , whereas the 41 naïve video viewers who predicted the play of same-sex conversation participants guessed at chance levels  (N = 19) were especially accurate , while males predicting the play of females (N = 10) were marginally accurate . For the informed video viewers, we did not find any sex interaction effects., P>0.9) . FemalesP>0.3; informed video viewers: δ±SE = −0.006±0.086, P>0.9) were no more accurate than predictions of the decisions made by conversation participants who were not facing the camera .Predictions of the PD decisions made by conversation participants facing the video camera  predicted that both their co-participants would make the same PD decision toward both that person's co-participants. In contrast, only 19/70 (27.1%) of naïve video viewers guessed that all three conversation participants would make the same PD decision toward both their co-participants. Five of 105 (4.8%) conversation participants predicted that both their co-participants made one decision to cooperate and one decision to defect, whereas 6/70 (8.6%) naïve video viewers predicted that all three conversation participants would make divergent decisions toward their two co-participants. Similarly, among the 35 informed video viewers, the mean (± SD) number of conversation participants (out of six) that were guessed to make consistent PD decisions toward both co-participants was 3.34±1.19. In fact, over 90% of conversation participants made the same PD decision toward both co-participants actors' unit-weighted frequencies of the four behaviors arms crossed, lean back, hand touch, and face touch  or other's guess of actor's PD decision toward him- or herself (for the 3rd party insiders) and (2) the frequency of DeSteno et al. actor.e models , 7, 8 vard party insiders were marginally more likely to guess cooperation when the recipient was more attractive, and informed video viewers were significantly influenced toward greater accuracy by the interaction between actor's primary psychopathy score and recipient's rate of interrupting actor, i.e. they expected actors higher in primary psychopathy to be less likely to cooperate toward recipients who had interrupted them more frequently.In general, the bivariate tests , and 5 srecipient's guess of actor's PD decision toward him/herself (2nd party guesses). Among recipients' guesses of actors' PD decisions toward themselves, 177/204 (86.8%) were concordant with the recipient's own PD decision toward that actor . Thus, it is unsurprising that recipient's PD decision toward actor massively predicts recipient's guess of actor's PD decision toward recipient. Models 2 and 4, which lack this independent variable, perform quite poorly at predicting recipient's guess of actor's PD decision. Within the multivariate models, the DeSteno et al. recipients' guesses, nor did their inclusion improve the predictive power of the models. Without the DeSteno et al. recipient's PD decision toward actor, recipients significantly expected actors higher in primary psychopathy to be more likely to cooperate toward them.others' guesses of actors' PD decisions toward recipients (3rd party insider guesses). Here, the models vary with respect to their inclusion, among the independent variables, of (1) others' guesses of actors' PD decisions toward themselves and (2) actors' DeSteno et al. other's prediction of actor's PD decision toward recipient was largely a function of other's prediction of actor's PD decision toward him- or herself. Controlling for the latter independent variable, others expected actors to be more likely to cooperate toward more attractive recipients. Within the multivariate models, the DeSteno et al. others' guesses, although they slightly improved the predictive power of the model that included, as an independent variable, other's prediction of actor's PD decision toward him- or herself.rd party outsider guesses). None of the models explained more than 3% of the variance in video viewers' guesses. Within the multivariate models, the DeSteno et al. actor's primary psychopathy score and the discovery of actor-recipient common ground, but in the opposite direction of the actual effect on game play: naïve video viewers expected that following the discovery of common ground, actors higher in primary psychopathy would be more likely to defect. Informed video viewers were influenced in the correct direction by the interaction between actor's primary psychopathy score and recipient's interruptions of actor: they expected actors higher in primary psychopathy to be more likely to defect toward recipients that had interrupted them more frequently.N = 176, o.r.  = 0.97±0.07, P>0.6) or we used individuals as data points and carried out an ordered logistic regression with a three-level dependent variable . The mean (±SD) unit-weighed DeSteno et al. Participants who displayed the DeSteno et al. When we added the DeSteno et al. In natural social life, judgments of others' propensities to cooperate occur under many different circumstances. Experimental work on defector-detection should seek to simulate a wide range of these contexts, to illuminate the scope and limits of whatever defector-detection mechanisms have evolved in humans. In this paper we add to existing literature by conducting a “small talk” session among participants, and only later introducing them to the prisoner's dilemma game. This resembles everyday first meetings between strangers who may later cooperate with each other, but still maintains experimental control by using an economic game. We coded conversational behavior, and used the game data, other self-report data and attractiveness ratings of participants to (1) assess the accuracy and the between-participant reliability of gameplay guesses and (2) document empirical predictors of the guesses themselves, and examine how these varied across types of judges. By comparing four categories of guessers – recipients of PD decisions, third party insiders, and naïve and informed outsiders – we accounted for the cognitive load of conversation participation, and for the importance of foreknowledge of the upcoming game.Conversation participants were no better than chance at predicting gameplay decisions. Our data suggest that this may be because participants base their predictions of an actor's play on their own decision toward that actor, and base third-party predictions largely on their second-party predictions for that actor. Although the first of these heuristics was erroneous, the second was generally valid—actors did tend to make the same decision toward both co-participants.In this study, as in DeSteno et al. We report elsewhere that socioeconomic status and subclinical psychopathy are predictive of players' choices to cooperate or defect higher in primary psychopathy. This supports the view We argue that participants are failing to predict defection because they are depending on a flawed folk model of defection, and not because they unable to detect relevant cues. Holding guessers' own PD decisions constant, we found that recipients were more likely to predict cooperation by co-participants who were Naïve video viewers, unlike conversation participants, approached better-than-chance prediction accuracy, and their cross-sex predictions were significantly more accurate than chance. The latter (unpredicted) result might reflect the operation of domain-specific mechanisms for detecting untrustworthiness in the opposite sex and thereby avoiding sexual exploitation . We are skeptical of this interpretation, because all conversation groups were single-sex—whereas such a domain-specific mechanism would likely require observation of between-sex interactions. Conversation participants rarely discussed romantic relationships, and almost all such discussion was brief and superficial. Moreover, ancestral humans presumably lived in groups in which intra-sexual cooperation and trustworthiness were comparable, in fitness-relevance, to intersexual cooperation and trustworthiness Naïve video viewers may be more accurate than conversation participants for several reasons. First, since video viewers made no PD decisions, they were free from the effects of cognitive dissonance reduction and false consensus beliefs. Video viewers were also free of the cognitive load entailed by the demands of self-presentation during a face-to-face interaction en face. Since facial expressions (particularly Duchenne smiles) are important for cooperator-detection en face player. This prediction received no support from our data, but perhaps video viewers' predictions were based on dyad-level rather than individual-level cues. This interpretation is consistent with our findings that video viewers were more likely than conversation participants to predict individually divergent PD decisions.Video viewers experienced the disadvantage of viewing only one person actor primary psychopathy interaction) was significant in the opposite direction of this variable's effect on actual PD decisions, and the main effect of recipient's interruptions of actor also trended in the opposite direction to that observed on PD decisions. Nor were they using the De Steno et al. The cues used by naïve video viewers in making their marginally accurate guesses remain a puzzle. They were not using a folk or implicit equivalent of the Gervais et al. Informed video viewers, who were presumably consciously seeking cues to post-conversation defection, failed to guess PD decisions at better-than-chance levels, and did not show the cross-sex effect found in naïve video viewers. These results are consistent with Bonnefon et al.'s Our results may be explained by the confluence of three attributes of the informed video viewer condition, which together impeded accurate social judgment: (1) the behavioral slices (10-min triadic conversations) were “thick” enough to provide input into a wide variety of social judgment heuristics, the relative weight of which varied among video viewers; (2) conversation participants were ignorant of the post-conversation PD and were therefore not deliberately displaying or eliciting signs of prosociality or trustworthiness; and (3) uniquely to the informed video viewer condition, video viewers were seeking such signs, and they varied in the extent to which they processed the difference between their own perspective (knowing about the post-conversation PD) and the uninformed perspective of the conversation participants. In other words, the perspective-taking task required of the informed video viewers may have been too demanding for participants to yield accurate judgments. Informed video viewers needed to (1) distinguish between their own knowledge and the conversation participants' ignorance of the PD and (2) if they viewed the PD as an assurance game Future research could determine whether individual variation in measures of social intelligence such as interpersonal sensitivity actors' frequencies of arms crossed, lean back, hand touch, and face touch as a cue of probability of defecting. Nor was actual defection associated with a higher frequency of engaging in this set of behaviors. We tentatively suggest four reasons for this failure to replicate the result of DeSteno et al. None of three independent sets of observers  used the unit-weighted average of Our results have implications for the study of the evolution of human cooperation. Naïve outsiders, but not interaction participants, were able to accurately judge inclinations to cooperate or defect, although it is likely that the observed levels of accuracy would be insufficient to support the evolution of one-shot cooperation under realistic assumptions about the benefit-to-cost ratio of cooperation


The aim of this study was to investigate the radioprotective effect of green tea against genotoxicity induced by gamma irradiation in cultured blood lymphocytes from 5 human volunteers.60 Co gamma irradiation and then were cultured with mitogenic stimulation to determine the chromosomal aberration in micronucleus assay on cytokinesis-blocked binucleated cells.Peripheral blood samples were collected from volunteers before and 1, 3 and 5 hr after drinking a decoction 4 g green tea in 280 ml boiling water for 5 constitutive days with the same quantity. At each time point, the whole blood samples were exposed to 200 cGy of As expected, for each volunteer, the results showed a significant increase in the incidence of micronuclei after exposure to gamma irradiation as compared to non-irradiated control samples. Only lymphocytes blood sample collected 3 hr after drinking green tea exhibited a significant decrease in incidence of micronuclei compared to non-treated irradiated samples.These results suggest the radioprotective ability of green tea against ionizing radiation in human lymphocytes, at specified time after consumptior. Intensional or unintentional irradiation due to radiotherapy during cancers or those caused by natural and industrial sources greatly damages the human tissues. Radiation exposure can induce damages either directly or indirectly to the genetic material of the cells. Indirect effects of radiation exposure are responsible for many biological damages to living tissues. The harmful effects of ionizing radiation are believed to be the result of interaction of free radicals with DNA or other cellular macromolecules , 2. Ioni Camellia sinensis, is the second most consumed beverage all over the world, well ahead of coffee and carbonated soft drinks. Among different teas, green tea has been chemically characterized; the water extract of green tea contains many polyphenols known as catechins that are known as antioxidants  with a dose of 200 cGy at a dose rate of 99.95 cGy/min. Subsequently, each sample (non-irradiated control and irradiated) was added to RPMI 1640 culture medium (Euroclone) supplemented by 20% fetal bovine serum (Gibco), 2% phytohaemagglutinin (Gibco), 100 µl/ml penicillin-streptomycin. Also, two cultures were set up, from each volunteer before drinking green tea, one left as non irradiated control and one was irradiated with the same dose of 99.95 cGy/min. All cultures were set up in duplicate and incubated at 37 °C in a humidified atmosphere of 5% CO2/95% air. Cytochalasin B  was added at 44 hr after culture initiation. At the end of 72 hr of incubation, the cells were collected according to Fenech  in 280 ml boiling water were steepened and drunk by each volunteer. Blood samples were collected in heparinized tubes from volunteers 1, 3 and 5 hr after drinking and at 1 hr after a daily doze of green tea for 5 constitutive days. At each sampling time, for each volunteer, 1 ml aliquots of heparinized whole blood was divided into two 25 ml culture flasks. One flask was the non-irradiated control sample and another was irradiated at 37 The statistical analysis was performed by the software MINITAB. And the data was presented as mean.P< 0.01). This suggests that drinking green tea does not induce any chromosomal damages. The results show the statistically significant increase in the frequency of micronucleated binucleates (MnBi) after irradiation in all samples (11.96±2.10) compared to non-irradiated control cells (P< 0.001). The percentage of micronuclei induced by gamma-irradiation in lymphocytes of all volunteers at 1, 3 and 5 hr after drinking of green tea was 10.24±2.86, 5.82±1.36 and 10.69±0.9, respectively. The frequency of Mn in binucleated lymphocytes of volunteers who has drunk green tea for five constitutive dayswas 12.84±1.57.The base line frequency of MnBi in non-irradiated blood lymphocytes from volunteers after drinking green tea at different time intervals before sampling were 0.06%±0.05 . This frP< 0.001). The result of green tea drinking at 1 and 5 hr before irradiation in both treatment schedules had no significant differences in their micronuclei with the non-treated irradiated lymphocytes. However, the lymphocytes in the blood samples were collected 3 hr after green tea drinking and were exposed in vitro to 200 cGy gamma-radiation. They exhibited a significant decrease in the incidence of micronuclei as compared to similarly non treated irradiated lymphocytes as well as other treated groups (P< 0.001). The total micronuclei values were 48.66% fold less 3 hr after green tea drinking (At all treatment schedules the frequency of micronucleated binucleates were statistically higher than in control group (drinking . These dAlthough many herbal preparations and compounds of plant origin have been evaluated as radioprotective agents in animals, there are few examples of experiments to demonstrate the efficacy of these extracts in human volunteers. A good radioprotective agent must provide different aspects for clinical applications, including effectiveness, low toxicity, availability, specificity and tolerance . Green tRegarding all the evidences about the antioxidant effect of green tea, the question remained unanswered is that whether drinking the green tea is able to protect the human cells from ionizing irradiation? In this study radioprotective effect of green tea was investigated.in vitro study on human lymphocytes with the same method of cytokinesis-blocked micronucleus assay, water soluble extract of green tea significantly reduced the X-ray induced Mn formation (Drinking of the green tea did not cause any chromosomal damages in human volunteers. However, it clearly reduced the frequency of chromosomal damages induced by gamma-irradiation. In an ormation . Chromosormation . The proormation , 11. Catormation . Short or long term drinking of green tea did not show any differences in its capability in reducing the chromosomal damages induced by gamma-irradiation in this study. There was a cell protection at only 3 hr post drinking. The peak plasma concentration of metabolite conjugates of catechins was reported to be around two hr post drinking , 28. TheThe results here suggest that green tea could be a useful candidate for protection of occupationally exposed individuals, such as those working in medical practice involving radiotherapy. For better protection one should drink green tea at around 2-3 hr before possible exposure. The data suggest that green tea could be a potential radioprotector when consumed 3 hr before irradiation. It could clearly reduce the gamma-induced chromosomal damages. This reduction in the frequency of micronuclei was not observed in other treatments.


Combined idiopathic pulmonary fibrosis (IPF) with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. While CPFE is a strong determinant of secondary precapillary pulmonary hypertension (PH), there is limited evidence regarding the management of patients with CPFE and PH.A 63 year-old male presented in 2006 with dyspnoea on exertion having quit smoking in 2003. Clinical examination, together with high resolution computed tomography, bronchoalveolar lavage, and echocardiographic assessments, suggested a diagnosis of CPFE without PH. In 2007, the patient received intravenous cyclophosphamide, N-acetylcysteine, and short-term anticoagulation treatment. Due to remission of acute exacerbations, the patient received triple combination therapy . Upon progressive clinical worsening, long-term supplemental oxygen therapy was initiated in 2009. Repeated right heart catheterisation in 2011 confirmed PH and worsening pulmonary haemodynamics, and off-label ambrisentan therapy was initiated. Dyspnoea remained at follow-up, although significant haemodynamic improvement was observed.CFPE is a distinct but under-recognized and common syndrome with a characteristic presentation. Further studies are needed to ascertain the etiology, morbidity, and mortality of CPEF with or without PH, and to evaluate novel management options. There is an increasing awareness of comorbid conditions frequently associated with idiopathic pulmonary fibrosis (IPF), including emphysema, cardiovascular disease, thromboembolic disease, and obstructive sleep apnoea. Recent retrospective data suggest that 21 to 33% of patients with IPF may have co-existing emphysema ,5 to accA 63 year-old man presented in 2006 with dyspnoea on exertion (New York Heart Association (NYHA) functional class II). He had smoked 20 pack-years and quit smoking in 2003, had no professional exposure, and had a history of hypercholesterolemia treated with atorvastatin, and surgery for prostatic adenocarcinoma followed by complete remission. Clinical examination demonstrated fine ’Velcro‘-like crackles of the lung bases, with no finger clubbing, and the absence of clinical signs of connective tissue disease. The patient’s body mass index was 25 kg/m².1) was 85% of predicted; the FEV1/FVC was 71%. Transfer capacity for carbon monoxide (DLco) was 72% and transfer coefficient was 81%. Partial arterial pressure of oxygen was 11.7 kPa, decreasing to 8.2 kPa with exercise. High resolution computed tomography (HRCT) of the chest demonstrated predominantly paraseptal emphysema of the upper zones of the lungs, and interstitial lung disease of the basal regions, with intralobular reticulation and ground glass opacities  of 91% of predicted, total lung capacity (TLC) of 79%, and a residual volume of 64%. Forced expiratory volume in one second  was initiated, with no change in oxygen saturation and PaOsyndrome with characteristic presentation, including very low diffusion capacity contrasting with subnormal spirometry, occurring in heavy smokers with severe dyspnoea and exercise limitation. It may be overlooked due to subnormal lung volumes, however gas exchanges are severely altered. Despite moderate or severe emphysema, a large proportion of patients with CPFE have FEV1/FVC >70% indicating that GOLD criteria for chronic obstructive lung disease may not be applicable [This patient case highlights a number of characteristics of the CPFE syndrome that contribute to distinctly different management compared with IPF alone (i.e. in the absence of emphysema). CPFE is a plicable . In addiplicable  and a hiplicable .A limited amount of data is available regarding lung pathology in patients with CPFE. Indeed, severe alteration of gas exchange and emphysema features at imaging may explain why lung biopsy is rarely performed, as in this presented case. A variety of pathology patterns of pulmonary fibrosis have been reported in patients with CPFE, including predominantly UIP pattern , however1 by 10% or more at 6 or 12 months may be useful in assessing disease progression [This case further indicates that the natural course of disease in CPFE may encompass episodes of acute exacerbation of pulmonary fibrosis, a complication seldom reported previously in CPFE. Further, the presence of significant emphysema impacts FVC measurement, and thus changes in FVC alone may not be a reliable indicator of disease ,12. Patigression , which cgression , which pgression . Whethergression . A compogression .There are currently no specific recommendations for the treatment of pulmonary fibrosis, emphysema or PH in the setting of CPFE. It is unknown whether treating these components of disease influences clinical outcomes. Patients with CPFE are likely to require long-term oxygen therapy. The presented case indicates that therapy specific for pulmonary hypertension may improve haemodynamics, as in other isolated reports ,16, but syndrome with characteristic presentation, and with a prognosis dominated by precapillary PH-associated with a poor prognosis, despite moderate haemodynamic severity. Further study is required regarding therapies targeting pulmonary fibrosis or PH.In conclusion, CPFE is a Vincent Cottin has received fees for speaking from Intermune, Boehringer Ingelheim, GSK, and Actelion, and has participated as a member of steering committees, a member of data safety monitoring boards or as an investigator to clinical trials sponsored by Actelion, Boehringer Ingelheim, Gilead, and Intermune Inc.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.


Malnutrition is a clinical condition due to the imbalance among needs, intake and use of nutrients, leading to the increase of morbidity and mortality, and to the impairment of quality of life. Even in industrialized countries undernutrition is becoming an alarming phenomenon, especially involving elderly institutionalized subjects.A multicentric study called PIMAI , was carried out in Italy over 2005. The aims of this study were to determine the prevalence of malnutrition in hospitals and in nursing care homes (NH), to assess the level of nutritional attention and to measure the perceived quality in food and nutritional care.This paper represents a preliminary analysis of data collected in a NH included in the PIMAI project.A total of 100 subjects , were recruited from January to June 2005 at the Clinical Rehabilitation Institute “Villa delle Querce” in Nemi (Rome), among patients in the NH facility. All the participants underwent a multidimensional geriatric evaluation , and a survey on “perceived quality” of nutritional care.According to nutritional status defined by the Mini Nutritional Assessment®, data analysis showed a high prevalence of malnutrition (36%) especially related to advanced age, chewing, cognitive and functional impairments. Patients seemed to consider nutrition to be important for their health; on the other hand, they were not thoroughly satisfied with the quality of food. Particularly, it was observed scarce attention to nutritional status from medical and nursing staff.Our study confirms the need to pay greater attention to nutritional status in elderly institutionalized subjects. Medical and nursing teams need to be aware of the importance to perform an evaluation of nutritional status in these subset of subjects. Protein- energy malnutrition (PEM) is a clinical condition due to the imbalance between needs, intake and utililization of nutrients, leading to increased morbidity and mortality, and to the impairment of quality of life In Europe, considering the time of admission to hospital, prevalence of PEM ranges from 10 to 80%, with an average value of 35% PEM is not easy to manage in elderly patients because of their frailty due to comorbidities, disability and socio- economic problems In spite of the recommendations delivered by Scientific Societies and the European Community Moreover, in elderly patients the effectiveness of nutritional interventions is reduced and the recovery from malnutrition is difficult to achieve Hence, malnutrition implies both direct and indirect high costs for National Health Services, the former linked to the condition itself, the latter due to the increased vulnerability, to repeated hospitalizations and to social reasons On the basis of all these remarks, a multicentric study called PIMAI , was carried out in Italy in 2005. The aims of the PIMAI study were to determine the prevalence of malnutrition in hospitals and in nursing care homes (NH), to assess the level of nutritional attention and to measure the perceived quality of food and nutritional care.Data related to the hospitals involved in the PIMAI study were analysed and published The study was performed in 100 subjects , who were recruited from January to June 2005 among resident patients in the nursing home facility at the Clinical Rehabilitation Institute “Villa delle Querce” in Nemi (Rome), which was one of the eleven PIMAI selected nursing homes throughout Italy. This facility is a level III nursing home, where, according to Italian Health Service organization, only patients with more severe functional impairment can be admitted.The study was approved by the Ethical Committee of the PIMAI coordinating centre  and written informed consent was obtained by participants or their legally authorized representatives.Random sampling from the daily list of new admissions was managed. All the subjects were considered eligible if they agreed to participate in the survey. Patients who presented with oedema, severe hepatic or renal failure, sepsis, or hypothyroidism, were excluded.The characteristics of the subjects enrolled are reported in All the enrolled subjects underwent a multidimensional evaluation, including the following aspects and parameters:demographic, social and cultural parameters: gender, age, civil status and education level;the nutritional status:Mini Nutritional Assessment (MNA®) was administered normal nutritional status: MNA score ≥24;risk of malnutrition: 17≤MNA score <23.5;malnutrition: MNA score <17;. In bedridden patients, body weight was measured using a bed- scale, while the height was estimated through KH.anthropometric parameters: body weight, height, arm circumference (AC), triceps skinfold thickness (TSF), calf circumference (CC), knee height (KH).2), muscle arm circumference [MAC = (AC- TSF)×π], and stature for bedridden subjects [stature = 94.87−(1.58×KH)−(0.23×age)+4.8 for men] were calculated The body mass index  The presence of partial or total edentulism and the presence and effectiveness of any dental prosthesis.The degree of impairment of normal food intake according to the following scale:normal orexia : 9–10 points;reduced orexia : from 8 to 6 points;poor orexia  from 5 to 3 points;anorexia : <3 points.Clinical status:The comorbidity level was assessed by the Geriatric Index of Comorbidity Class I: patients with one or more asymptomatic diseases at a subclinical stage or successfully treated diseases in the past;Class II: one or more diseases with mild to moderate symptoms controlled by treatment;Class III: one or more diseases with severe symptoms poorly controlled by treatment;Class IV: one or more of these diseases at the maximum level of severity, not controlled by treatment;The definition of the severity of each disease was determined according to the Index of Disease Severity of Greenfield Past medical history and number of current medications;The presence of symptoms potentially interfering with feeding: gastrointestinal symptoms , and pain, that was defined using the following modified version of the Oswestry Low Back Pain Disability Questionnaire I can tolerate the pain I have without having to use drugs;the pain is bad, but I can manage without having to take drugs;drugs provides me with complete relief from pain;drugs provides me with moderate relief from pain;drugs provides me with little relief from pain;drugs has no effect on my pain.Cognitive status and depression, respectively assessed using the SPMSQ-Short Portable Mental Status Questionnaire (SPMSQ) Functional abilities were measured using the Karnofsky performance status test Laboratory parameters: total protein content, albumin, transferrin, prealbumin, red blood cells count, hemoglobin, hematocrit, mean corpuscular volume, white blood cell count, lymphocytes count, C-Reactive Protein (CRP), mucoproteins, cholesterol, and cholinesterase levels were tested. Biochemical assays were performed at the ICR of “Villa delle Querce Nemi” (Rome) using commercial kits supplied by ABX Italy (Rome). A COBAS- MIRA analyser was used. Blood samples were obtained from the antecubital vein after an overnight fast.A survey about the “perceived quality” of nutritional assistance, food and diet was carried out 3 days after the admission, using a structured interview , includi2 test) were performed. Statistical significance was set at p value<0.05.Nutritional status was correlated with other clinical and functional potential explanatory variables. After verification of the normal distribution of the variables, parametric tests for comparison of means (Student's t-test and ANOVA) and tests for the evaluation of the frequency distribution .Data analysis included all the 100 subjects recruited between January and June 2005 among resident patients in the nursing home facility at the Clinical Rehabilitation Institute “Villa delle Querce” in Nemi (Rome). Males subjects were slightly but not significantly younger than females .Overall, accordingly to MNA®, prevalence of malnutrition was 36%; 46% of subjects were at risk of malnutrition, while the nutritional status was found to be normal only in 18% of participants. The prevalence was similar in both genders. About 12% of subjects lost at least 1 kg of body weight in the last three months, while more than 30% of subjects were obese .15, data analysis showed the following results:Accordingly to the nutritional status defined with the MNA®social and cultural parameters . Regarding social and cultural parameters, loneliness, poverty and a low educational level Data in our study confirm that ageing- induced malnutrition is usually secondary to a decrease in appetite and in food intake Regarding difficulties in chewing, we demonstrated that 41.7% of the malnourished subjects had a reduced food intake, 86.1% were partially edentulous and 76.5% had ineffective dental prosthesis. Some studies Disability and cognitive impairment are further potential causes of malnutrition The level of autonomy was assessed with three instruments: Karnofsky performance status test, activities daily living (ADL) test and instrumental activities of daily living (IADL) test. Malnourished subjects seemed to have a greater level of disability in activities of daily living and with frequent requests of nursing assistance and medical care (as verified by the Karnofsky test score). These data are indirectly confirmed by the handgrip strength test, that showed deeply reduced values in malnourished subjects . These results are in line with existing literature: in most studies, disability is associated to biochemical and anthropometric parameters related to malnutrition, to the need for assistance and home care and to a longer stay in health care facilities Similarly, the mental state may affect nutritional status and cognitive impairment is more common in malnourished than well-nourished subjects In several studies, depression is considered to be a risk factor for malnutrition and vice versa Previous studies of our group highlighted a relationship between nutritional status and comorbidity ad hoc questionnaire was created for the PIMAI project consisting of sixteen questions focused on the catering service and medical/nursing care dedicated to nutritional aspects. Our data show no statistically significant differences for these parameters in relation to nutritional status. Anyway, while considering food important for their health status, patients were not totally satisfied of the quality of diet in the NH. They also noticed a low attention paid to nutritional status from medical and nursing staff. Few studies in the literature dealt with the surveys on the perceived quality of diet and on the counseling received about nutrition in nursing homes. Lengyel et al. Improvement of the quality of life for residents in healthcare facilities may be achieved through the identification of critical points concerning in particular the quality of the catering service and the perceived quality of medical and nursing care A limitation of the present study was the small sample size. The whole analysis of data collected in the full database of the PIMAI project will give further and more complete information. Another limitation is the setting of enrollment: our subjects were enrolled in a level III nursing home, where, according to Italian Health Service organization, only patients with more severe functional impairment can be admitted.Finally, the present study stresses the need to pay greater attention to nutritional status in elderly institutionalized subjects. Medical and nursing staff need to be aware of the importance to perform the evaluation of nutritional status  in this subset of subjects and to consider, in particular, cognitive and functional performances as risk factors for malnutrition. Patients seem to be aware of the role of nutritional status in their life and they ask for a more precise nutritional care and an improved quality of catering services. Individual factors play a pivotal role in malnutrition; on the other hand it has to be stressed that in nursing homes several organizational aspects work negatively influencing indirectly the onset or the worsening of malnutrition: for example, the amount of nursing staff available during meals to provide feeding assistance is crucial. Hence, multilevel models of analysis should be prompted in order to better evaluate the relevance of organizational features in terms of prevention and care of malnutrition in nursing home residents.Therefore, the management of hospitals and nursing homes should take into account the quality of catering services as a way to improve nutritional and health status of elderly institutionalized subjects.


To investigate the clinical rationale and agreement between raters for making Ayurvedic diagnoses, using a mixed methods approach.Three 30 minute Ayurvedic assessments, including a history and limited physical exam, were videotaped and then viewed by Ayurvedic clinicians. The clinicians were asked to identify the primary and secondary dosha (Ayurvedic physiologic principle) involved in the patient’s prakruti (mind-body constitution) and vikruti (current state of the doshas) and explain their rationale for making a diagnosis. Cross-sectional comparison and thematic analytic approaches were used to analyze qualitative data.Of 13 participants to date, 77% had at least a 6-year Bachelor of Ayurvedic Medicine and Surgery degree; participants had a mean of 15 years of clinical experience. Overall agreement on diagnoses ranged between 60-100% and was higher for vikruti (mean 86%) than prakruti (mean 75%). The mean rating of the similarity of the video format to real life was five . Qualitative themes reported were: 1) Participants felt the video format limited their ability to ask about specific clinical information. 2) Participants explained that the video format was limiting because more clinical details obtained in a longer interview, an in-person physical exam, and re-evaluation of findings over time are important in making an accurate prakruti diagnosis.A moderate to high degree of agreement was found in the quantitative analysis and was better for vikruti than prakruti diagnoses. The video format, though well suited to the research paradigm, was limiting for the clinicians in terms of real world practice. Even when there was disagreement in diagnoses, the clinical rationale provided by clinicians was consistent with the theoretical basis of Ayurvedic medicine. A mixed methods approach was well suited to the study of Ayurveda as a whole system of medicine, but whole systems research remains challenging due to the complexity of the whole system.