Deployment of AMMI, GGE-biplot and MTSI to select elite genotypes of castor (Ricinus communis L.).

Castor (Ricinus communis L.) is an important industrial multipurpose non-edible oilseed C3 crop belongs to spurge family popularly known as Euphorbiaceae. Its oil has exceptional properties which provides an industrial importance to this crop. The present investigation is aimed to judge the stability and performance of yield and yield assigning traits and selection of suitable genotype for varied locality of western rainfed regions of India. During the study with 90 genotypes, the genotype × environment interaction was found to be significant for seed yield per plant as well as for plant height up to primary raceme, total length of primary raceme, effective length of primary raceme, capsules on main raceme and effective number of racemes per plant. E1 is the least interactive and highly representative site for seed yield. Which won where and what biplot decipher ANDCI 10-01 as vertex genotype for E3 while ANDCI 10-03 and P3141 for E1 and E2. Average Environment co-ordinate identify ANDCI 10-01, P3141, P3161, JI 357 and JI 418 as tremendously stable and high seed yielding genotypes. The study outlined the pertinency of Multi Trait Stability Index, that calculated based on the genotype-ideotype distance as the multiple interacting variables. MTSI evaluated all genotypes and sort ANDCI 12-01, JI 413, JI 434, JI 380, P3141, ANDCI 10-03, SKI 215, ANDCI 09, SI 04, JI 437, JI 440, RG 3570, JI 417 and GAC 11 with maximum stability and high mean performance of analyzed interacting traits.

Prevalence and characteristics of eating disorders among college students of a nonmetro city of Gujarat.

Context: There is a relative paucity of prevalence data about eating disorders (EDs) in India among young population. Aims: We aimed to estimate the prevalence and characteristics of EDs and abnormal eating behaviors among college students of a nonmetro city of Gujarat. Setting and Design: A cross-sectional survey was done among five colleges of a nonmetro city in Gujarat from February to September 2019. Subjects and Methods: Total 790 college students were assessed using a semi-structured format, Eating Attitudes Test-26, and Bulimic Investigatory Test Edinburgh followed by structured clinical interview as per DSM-5 criteria for EDs. Statistical Analysis: Outcomes were expressed in frequency, proportion, mean, and standard deviation. P values were calculated by Pearson Chi-square test or Fisher's exact test to determine the significance of the result. Results: The prevalence of abnormal eating behaviors was 25.2% (n = 199). Anorexia nervosa (AN) was not detected. The prevalence of bulimia nervosa (BN) was 0.2% and other specified feeding or eating disorder (OSFED) was 0.6%. "Being aware of calorie content" (53.7%) and "preoccupation with desire of thinness" (46.3%) were commonly found. "Impulse to vomit after meals" (2.5%) was least common. Lower body mass index was found among subjects with abnormal eating behavior. None of the subjects had amenorrhea. Conclusions: The prevalence of disordered eating behaviors, BN, and OSFED was 25.2%, 0.2%, and 0.6%, respectively. AN was not detected. OSFED was the most common ED and the characteristic "body image disturbance" was the most common symptom.

Carbazole-based semicarbazones and hydrazones as multifunctional anti-Alzheimer agents.

With the aim to combat a multi-faceted neurodegenerative Alzheimer's disease (AD), a series of carbazole-based semicarbazide and hydrazide derivatives were designed, synthesized and assessed for their cholinesterase (ChE) inhibitory, antioxidant and biometal chelating activity. Among them, (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(pyridin-2-yl)hydrazinecarbothioamide (62) and (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(5-chloropyridin-2-yl)hydrazinecarbothioamide (63) emerged as the premier candidates with good ChE inhibitory activities (IC50 values of 1.37 µM and 1.18 µM for hAChE, IC50 values of 2.69 µM and 3.31 µM for EqBuChE, respectively). All the test compounds displayed excellent antioxidant activity (reduction percentage of DPPH values for compounds (62) and (63) were 85.67% and 84.49%, respectively at 100 µM concentration). Compounds (62) and (63) conferred specific copper ion chelating property in metal chelation study. Molecular docking studies of compounds (62) and (63) indicate strong interactions within the active sites of both the ChE enzymes. Besides that, these compounds also exhibited significant in silico drug-like pharmacokinetic properties. Thus, taken together, they can serve as a starting point in the designing of multifunctional ligands in pursuit of potential anti-AD agents that might further prevent the progression of ADs.Communicated by Ramaswamy H. Sarma.

Further Studies on Triazinoindoles as Potential Novel Multitarget-Directed Anti-Alzheimer's Agents.

The inadequate clinical efficacy of the present anti-Alzheimer's disease (AD) drugs and their low impact on the progression of Alzheimer's disease in patients have revised the research focus from single targets to multitarget-directed ligands. A novel series of substituted triazinoindole derivatives were obtained by introducing various substituents on the indole ring for the development of multitarget-directed ligands as anti-AD agents. The experimental data indicated that some of these compounds exhibited significant anti-AD properties. Among them, 8-(piperidin-1-yl)-N-(6-(pyrrolidin-1-yl)hexyl)-5H-[1,2,4]triazino[5,6-b]indol-3-amine (60), the most potent cholinesterase inhibitor (AChE, IC50 value of 0.32 µM; BuChE, IC50 value of 0.21 µM), was also found to possess significant self-mediated Aß1-42 aggregation inhibitory activity (54% at 25 µM concentration). Additionally, compound 60 showed strong antioxidant activity. In the PAMPA assay, compound 60 exhibited blood-brain barrier penetrating ability. An acute toxicity study in rats demonstrated no sign of toxicity at doses up to 2000 mg/kg. Furthermore, compound 60 significantly restored the cognitive deficits in the scopolamine-induced mice model and Aß1-42-induced rat model. In the in silico ADMET prediction studies, the compound satisfied all the parameters of CNS acting drugs. These results highlighted the potential of compound 60 to be a promising multitarget-directed ligand for the development of potential anti-AD drugs.

Novel carbazole-stilbene hybrids as multifunctional anti-Alzheimer agents.

Molecules capable of engaging with multiple targets associated with pathological condition of Alzheimer's disease have proved to be potential anti-Alzheimer's agents. In our goal to develop multitarget-directed ligands for the treatment of Alzheimer's disease, a novel series of carbazole-based stilbene derivatives were designed by the fusion of carbazole ring with stilbene scaffold. The designed compounds were synthesized and evaluated for their anti-AD activities including cholinesterase inhibition, Aß aggregation inhibition, antioxidant and metal chelation properties. Amongst them, (E)-1-(4-(2-(9-ethyl-9H-carbazol-3-yl)vinyl)phenyl)-3-(2-(pyrrolidin-1-yl)ethyl)thiourea (50) appeared to be the best candidate with good inhibitory activities against AChE (IC50 value of 2.64 µM) and BuChE (IC50 value of 1.29 µM), and significant inhibition of self-mediated Aß1-42 aggregation (51.29% at 25 µM concentration). The metal chelation study showed that compound (50) possessed specific copper ion chelating property. Additionally, compound (50) exhibited moderate antioxidant activity. To understand the binding mode of 50, molecular docking studies were performed, and the results indicated strong non-covalent interactions of 50 with the enzymes in the active sites of AChE, BuChE as well as of the Aß1-42 peptide. Additionally, it showed promising in silico ADMET properties. Putting together, these findings evidently showed compound (50) as a potential multitarget-directed ligand in the course of developing novel anti-AD drugs.

Predictors of problematic Internet use in school going adolescents of Bhavnagar, India.

BACKGROUND: Problematic Internet use (PIU) is the inability of individuals to control their Internet use, resulting in marked distress and/or functional impairment in daily life. AIM/OBJECTIVE: We assessed the frequency of PIU and predictors of PIU, including social anxiety disorder (SAD), quality of sleep, quality of life and Internet-related demographic variables among school going adolescents. METHODS: This was an observational, single-centered, cross-sectional, questionnaire-based study of 1,312 school going adolescents studying in Grades 10, 11 and 12 in Bhavnagar, India. Every participant was assessed by a pro forma containing demographic details, questionnaires of Internet Addiction Test (IAT), Social Phobia Inventory (SPIN), Pittsburgh Sleep Quality Index (PSQI) and Satisfaction With Life Scale (SWLS) for PIU severity, SAD severity, Quality of Sleep assessment and Quality of Life assessment, respectively. The statistical analysis was done with SPSS Version 23 (IBM Corporation) using chi-square test, Student's t test and Pearson's correlation. Multiple linear regression analysis was applied to find the predictors of PIU. RESULTS: We found frequency of PIUs as 16.7% and Internet addiction as 3.0% among school going adolescents. Participants with PIU are more likely to experience SAD ( p < .0001), poor quality of sleep ( p < .0001) and poor quality of life ( p < .0001). There is positive correlation between severity of PIU and SAD ( r = .411, p < .0001). Linear regression analysis shows PIU can be predicted by SAD, sleep quality, quality of life, English medium, male gender, total duration of Internet use, monthly cost of Internet use, education, social networking, gaming, online shopping and entertainment as purpose of Internet use. CONCLUSION: Participants with PIU are more likely to experience SAD, poor quality of sleep and poor quality of life.

DNA methylation patterns of adult survivors of adolescent/young adult Hodgkin lymphoma compared to their unaffected monozygotic twin.

DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from long-term AYAHL survivors and their unaffected co-twins. Epigenetic aging (DNAm age) was calculated using previously described methods and compared between survivors and co-twins using paired t-tests and analyses were stratified by sample type, histology, sex, age at sample collection and time since diagnosis. Differences in blood DNAm age were observed between survivors and unaffected co-twins (64.1 vs. 61.3 years, respectively, p = .04), especially in females (p = .01); no differences in saliva DNAm age were observed. Survivors and co-twins had 74 (in blood DNA) and 6 (in saliva DNA) differentially methylated loci. Our results suggest persistent epigenetic aging in AYAHL survivors long after HL cure.

Follicular large cleaved cell (centrocytic) lymphoma: an unrecognized variant of follicular lymphoma.

The World Health Organization classification of lymphoma recommends the subdivision of follicular lymphoma (FL) into 3 grades (FL1-3) based on the average number of centroblasts per high-power field in the neoplastic follicles, but does not recognize a form of FL characterized by a predominance of large cleaved cells (centrocytes) without enough centroblasts to meet the World Health Organization criteria for FL3. We have classified such cases as follicular large cleaved cell lymphoma (FLC) and, herein, describe the pathologic and clinical features of 72 cases of this entity. The features of FLC include a follicular growth pattern with pale follicles at low magnification and frequent follicular and/or interfollicular fibrosis. Cytologically, the cells are predominantly large cleaved cells with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear diameter of the large cleaved cells was 10.1µ, approximately twice that of small lymphocytes and similar to centroblasts. The t(14;18) was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%) and had high Ki67 proliferation (81%). The clinical features of patients with FLC were similar to those with other types of FL, and survival was excellent with anthracycline-based chemotherapy plus rituximab. FLC is a variant of follicular lymphoma which should be recognized in future lymphoma classifications because the diagnosis of FLC may be important for the selection of therapy.

Twelve-month prevalence and treatment gap for common mental disorders: Findings from a large-scale epidemiological survey in India.

BACKGROUND: Common mental disorders, such as mood, anxiety, and substance use disorders, are significant contributors to disability globally, including India. Available research is, however, limited by methodological issues and heterogeneities. AIM: The present paper focuses on the 12-month prevalence and 12-month treatment for anxiety, mood, and substance use disorders in India. MATERIALS AND METHODS: As part of the World Health Organization World Mental Health (WMH) Survey Initiative, in India, the study was conducted at eleven sites. However, the current study focuses on the household sample of 24,371 adults (≥18 years) of eight districts of different states, covering rural and urban areas. Respondents were interviewed face-to-face using the WMH Composite International Diagnostic Interview after translation and country-specific adaptations. Diagnoses were generated as per the International Classification of Diseases, 10th edition, Diagnostic Criteria for Research. RESULTS: Nearly 49.3% of the sample included males. The 12-month prevalence of common mental disorders was 5.52% - anxiety disorders (3.41%), mood disorders (1.44%), and substance use disorders (1.18%). Females had a relatively higher prevalence of anxiety and mood disorders, and lower prevalence of substance use disorders than males. The 12-month treatment for people with common mental disorders was 5.09% (range 1.66%-11.55% for individual disorders). The survey revealed a huge treatment gap of 95%, with only 5 out of 100 individuals with common mental disorders receiving any treatment over the past year. CONCLUSION: The survey provides valuable data to understand the mental health needs and treatment gaps in the Indian population. Despite the 12-month prevalence study being restricted to selected mental disorders, these estimates are likely to be conservative due to under-reporting or inadequate detection due to cultural factors.

Selection of DNA aptamers with two modified bases.

The nucleobases comprising DNA and RNA aptamers provide considerably less chemical diversity than protein-based ligands, limiting their versatility. The introduction of novel functional groups at just one of the four bases in modified aptamers has recently led to dramatic improvement in the success rate of identifying nucleic acid ligands to protein targets. Here we explore the benefits of additional enhancement in physicochemical diversity by selecting modified DNA aptamers that contain amino-acid-like modifications on both pyrimidine bases. Using proprotein convertase subtilisin/kexin type 9 as a representative protein target, we identify specific pairwise combinations of modifications that result in higher affinity, metabolic stability, and inhibitory potency compared with aptamers with single modifications. Such doubly modified aptamers are also more likely to be encoded in shorter sequences and occupy nonoverlapping epitopes more frequently than aptamers with single modifications. These highly modified DNA aptamers have broad utility in research, diagnostic, and therapeutic applications.

Non-Hodgkin lymphoma in Romania: a single-centre experience.

Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd.

Cyclin D1 expression in peripheral T-cell lymphomas.

Cyclin D1 is an important regulator of the cell cycle and overexpression of this protein by immunohistochemistry is characteristically seen in mantle cell lymphoma and other B-cell neoplasms. However, little is known about the expression of this protein in T-cell lymphomas. Cyclin-dependent kinase pathway inhibitors are in development, therefore identifying cyclin D1-positive T-cell lymphomas may provide a therapeutic target in a disease where novel treatments are urgently needed. We collected 200 peripheral T-cell lymphomas from three institutions including the following types of cases: 34 anaplastic large cell lymphoma, ALK+, 44 anaplastic large cell lymphoma, ALK negative, 68 peripheral T-cell lymphomas, not otherwise specified, 24 angioimmunoblastic T-cell lymphomas, 7 extranodal NK/T-cell lymphomas, 4 enteropathy associated T-cell lymphomas, 3 hepatosplenic T-cell lymphomas, 12 cutaneous T-cell lymphomas, and 4 large granular lymphocytic leukemias. Immunohistochemical stains for cyclin D1 protein (SP4 clone) were performed on paraffin-embedded tissue. In a subset of cases, IGH/CCND1 fluorescence in situ hybridization analysis was also performed. Cyclin D1 staining was predominantly seen in anaplastic large cell lymphoma, including 8 of 34 cases with ALK+ anaplastic large cell lymphoma (24%), and 3 of 44 cases of ALK-negative (7%) anaplastic large cell lymphoma. Three cases of peripheral T-cell lymphoma, not otherwise specified, were also positive (3/68, 4%). All other T-cell lymphomas were negative for cyclin D1. In four of the cyclin D1-positive T-cell lymphomas by immunohistochemistry, fluorescence in situ hybridization analysis was negative for IGH/CCND1 translocation or extra copies of the CCND1 gene. Cyclin D1 overexpression by immunohistochemistry is not limited to B-cell lymphomas and is also observed in some peripheral T-cell lymphomas, particularly in anaplastic large cell lymphoma, ALK+. Cyclin D1 expression was not associated with extra copies or translocation of the CCND1 gene. Cyclin D1 overexpression may be the result of a post-translational phenomenon and may represent a potential therapeutic target using agents that target the cyclin-dependent kinase pathway.

Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project.

The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 26 centers in 24 countries using the World Health Organization classification, and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males than females in the developing regions compared to the developed world (P<0.05). The median age at diagnosis was significantly lower for both low- and high-grade B-cell lymphoma in the developing regions. The developing regions had a significantly lower frequency of B-cell lymphoma (86.6%) and a higher frequency of T- and natural killer-cell lymphoma (13.4%) compared to the developed world (90.7% and 9.3%, respectively). Also, the developing regions had significantly more cases of high-grade B-cell lymphoma (59.6%) and fewer cases of low-grade B-cell lymphoma (22.7%) compared to the developed world (39.2% and 32.7%, respectively). Among the B-cell lymphomas, diffuse large B-cell lymphoma was the most common subtype (42.5%) in the developing regions. Burkitt lymphoma (2.2%), precursor B- and T-lymphoblastic leukemia/lymphoma (1.1% and 2.9%, respectively) and extranodal natural killer/T-cell lymphoma (2.2%) were also significantly increased in the developing regions. These findings suggest that differences in etiologic and host risk factors are likely responsible, and more detailed epidemiological studies are needed to better understand these differences.

Non-Hodgkin lymphoma in Southern Africa: review of 487 cases from The International Non-Hodgkin Lymphoma Classification Project.

Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low-grade (LG) B-NHL (34·3%) and a higher proportion of high-grade (HG) B-NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High-grade Burkitt-like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60·4%) and a lower frequency of HG B-NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B-NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences.

Relative frequency of non-Hodgkin lymphoma subtypes in selected centres in North Africa, the middle east and India: a review of 971 cases.

Comparative data regarding the distribution of non-Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly-diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91·7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male-to-female ratio was significantly higher in NAF/ME/IN (1·8) compared to NA (1·1; P< 0·05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B-NHL (28·4%) and a higher proportion of HG B-NHL (58·4%) were found compared to NA (56·1% and 34·3%, respectively). Diffuse large B-cell lymphoma was more common in NAF/ME/IN (49·4%) compared to NA (29·3%), whereas follicular lymphoma was less common in NAF/ME/IN (12·4%) than in NA (33·6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences.

Non-Hodgkin lymphoma in the Far East: review of 730 cases from the international non-Hodgkin lymphoma classification project.

Large and systematic studies of non-Hodgkin lymphoma (NHL) in the Far East (FE) with good comparative data are scarce in the literature. In this study, five expert hematopathologists classified 730 consecutive cases of newly-diagnosed NHL from four sites in the FE (excluding Japan) using the World Health Organization classification. The results were compared to 399 cases from North America (NA). We found a significantly higher male to female ratio in the FE compared to NA (1.7 versus 1.1; p < 0.05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in the FE (58 and 51 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). The FE had a significantly lower relative frequency of B-NHL and a higher frequency of T-NHL (82 vs. 18 %) compared to NA (90.5 vs. 9.5 %). Among mature B cell lymphomas, the FE had a significantly higher relative frequency of HG B-NHL (54.8 %) and a lower frequency of LG B-NHL (27.2 %) than NA (34.3 and 56.1 %, respectively). Diffuse large B cell lymphoma was more common in the FE (49.4 %) compared to NA (29.3 %), whereas the relative frequency of follicular lymphoma was lower in the FE (9.4 %) compared to NA (33.6 %). Among T-NHL, nasal NK/T cell NHL was more frequent in the FE (5.2 %) compared to NA (0 %). Peripheral T cell lymphoma was also more common in the FE (9.1 %) than in NA (5.3 %). Further epidemiologic studies are needed to better understand the pathobiology of these differences.

Common immune-related exposures/conditions and risk of non-Hodgkin lymphoma: a case-control study of disease-discordant twin pairs.

We evaluated the association between common immune system-altering experiences and non-Hodgkin lymphoma (NHL) risk using a case-control study of 162 like-sex twin pairs discordant for NHL, identified from the International Twin Study. Information on medical history and evidence of childhood exposure to microbes was obtained by questionnaire from 1998 to 2002. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Intra-twin-pair agreement between twins on individual exposures was high (76%-97%). A negative association between NHL and seasonal hay fever (odds ratio (OR) = 0.28, 95% confidence interval (CI): 0.10, 0.75) and certain allergies (OR = 0.29, 95% CI: 0.13, 0.68) was observed. The number of atopic diseases was negatively associated with NHL (P for trend = 0.0003). A history of infectious mononucleosis was negatively associated with NHL risk (OR = 0.35, 95% CI: 0.14, 0.90). NHL risk was associated with more frequent childhood exposure to microbes during early life (P for trend = 0.04). No differences in association by NHL subtype were observed, although statistical power for these comparisons was low. These observations support the hypothesis that immune-related exposures, especially atopy, are associated with decreased NHL risk. Use of the within-twin-pair study design mitigates confounding by genome, family structure, and unmeasured characteristics of early childhood factors.

Classification of non-Hodgkin lymphoma in South-eastern Europe: review of 632 cases from the international non-Hodgkin lymphoma classification project.

The distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world, but a systematic study of South-eastern Europe (SEEU) has never been done. Therefore, we evaluated the relative frequencies of NHL subtypes in three SEEU countries--Croatia, Romania and Macedonia. Five expert haematopathologists reviewed 632 consecutive cases of newly diagnosed NHL from the three SEEU countries using the World Health Organization classification. The results were compared to 399 cases from North America (NA) and 580 cases from Western Europe (WEU). The proportions of B- and T-cell NHL and the sex distribution in SEEU were similar to WEU and NA. However, the median ages of patients with low- and high-grade B-NHL in SEEU (60 and 59 years, respectively) were significantly lower than in NA (64 and 68 years, respectively; P < 0·05). SEEU had a significantly lower proportion of low-grade B-NHL (46·6%) and higher proportion of high-grade B-NHL (44·5%) compared to both WEU (54·5% and 36·4%, respectively) and NA (56·1% and 34·3%, respectively). There were no significant differences in the relative frequencies of T-NHL subtypes. This study provides new insights into differences in the relative frequencies of NHL subtypes in different geographic regions. Epidemiological studies are needed to better characterize and explain these differences.