Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone.

Giant cell tumor of bone typically involves the epiphysis of the long bones of skeletally mature patients. It is genetically characterized by highly recurrent and specific mutations of the H3F3A gene, which encodes histone H3.3. The most common mutation H3F3A G34W can readily be detected by a recently developed mutation-specific antibody. Giant cell tumor of bone rarely transforms to a sarcoma (malignant giant cell tumor of bone), which has not been genetically characterized in detail. We studied seven clinicopathologically defined malignant giant cell tumors, as well as two H3F3A-mutant bone sarcomas without giant cell tumor histology using a combination of clinicopathological, immunohistochemical, and molecular methods (Sanger sequencing + pyrosequencing or next generation sequencing). The cases included five men and four women, with a median age at initial diagnosis of 27 years. The two H3F3A G34W-positive sarcomas without giant cell tumor histology involved the subarticular epiphyseal sites, suggesting relatedness with giant cell tumor of bone. In two of the seven clinicopathologically defined malignant giant cell tumor cases, the sarcoma tissue showed the H3F3A G34W mutation. However, in the remaining five cases, in contrast to their associated H3F3A G34W-mutant giant cell tumor, the sarcoma lacked the H3F3A G34W mutation, either entirely or sub-clonally in the samples tested. This discordant mutation status was confirmed in all instances by immunohistochemistry and sequencing. A FISH analysis suggested that the absence of the H3F3A G34W mutation may be related to deletion of the H3F3A gene. Therefore, we have demonstrated that H3F3A G34W mutation, a critical driver in giant cell tumor, is absent in a subset of malignant giant cell tumor of bone. This novel recurrent phenomenon has potential biological and diagnostic implications, and further study is required to better characterize this progression pathway and understand its mechanism.

KMT2A (MLL) fusions in aggressive sarcomas in young adults.

AIM: To characterise unclassifiable sarcomas by use of a combined histological and molecular approach. METHODS AND RESULTS: Using RNA sequencing, we identified in-frame fusions involving KMT2A (MLL) in two cases. Case 1 was a 20-year-old woman with a deep soft tissue mass in the thigh. The tumour consisted of monomorphic round, epithelioid and spindle cells in a highly sclerotic background that were focally immunopositive for CD34, CD31, and ERG. Case 2 was a 30-year-old woman with a tumour that affected the femur and surrounding soft tissue. The tumour consisted of monomorphic round to spindle cells that were immunopositive for BCOR, Wilms tumour 1, and NKX2-2. Both tumours were aggressive and had metastasised to the lung; both patients died within a few years. RNA sequencing identified a YAP1 (exon 5)-KMT2A (exon 4) fusion in case 1 and a VIM (exon 4)-KMT2A (exon 2) fusion in case 2, both of which were confirmed by reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in-situ hybridisation. The fusion protein structure was different from that in acute leukaemia, suggesting a novel oncogenic mechanism. CONCLUSIONS: KMT2A fusions account for a subset of aggressive unclassifiable sarcomas in young adults. Although it is presently unclear whether these sarcomas belong to a single group, the well-established role of KMT2A fusions as drivers of acute leukaemia and a recent publication regarding identification of YAP1-KMT2A in one unclassifiable sarcoma support the significance of these fusions. Further studies on additional cases are necessary to fully understand the clinicopathological and molecular aspects of KMT2A-rearranged sarcomas.

INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcoma is a rare subtype of sarcoma that affects the soft tissue and bones in middle-aged and elderly adults. Its diagnosis can be challenging, with the differential diagnoses including a wide variety of mesenchymal tumors. The line of differentiation of extraskeletal myxoid chondrosarcoma has been controversial, but recent evidence suggests a neuroendocrine phenotype. INSM1 is a zinc-finger transcription factor that plays a pivotal role in neuroendocrine differentiation, and has been proposed as a promising immunohistochemical marker of neuroendocrine carcinoma. The aim of this study was to determine the prevalence of INSM1 expression in extraskeletal myxoid chondrosarcoma and to understand its significance in sarcoma diagnosis. We immunostained the representative sections of 31 NR4A3-rearranged extraskeletal myxoid chondrosarcomas and 187 histological mimics. Nuclear staining of moderate or higher intensity in at least 5% of tumor cells was considered positive. Twenty-eight of the 31 extraskeletal myxoid chondrosarcomas (90%) were positive for INSM1, providing strong evidence for neuroendocrine differentiation. The staining was diffuse (>50%) in 17 cases, with most immunopositive tumors showing at least focal strong expression. The INSM1 staining extent was not correlated with cytomorphology, synaptophysin expression, or fusion types (EWSR1 vs non-EWSR1). In contrast, INSM1 expression was negative in 94% of the 187 other mesenchymal tumors. INSM1-positive mimics comprised a small subset of chordoma (1 of 10), soft tissue myoepithelioma (1 of 20), ossifying fibromyxoid tumor (3 of 10), and Ewing sarcoma (3 of 10), among other tumor types. The majority of these cases showed labeling in <25% of the tumor cells. Although not entirely sensitive or specific, INSM1 could be a potential marker for the diagnosis of extraskeletal myxoid chondrosarcoma when molecular genetic access is limited.

PAX7 immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours.

AIMS: Ewing sarcoma is a small round cell tumour that affects bone and soft tissues. Although the detection of the specific fusion gene is a robust method of its diagnosis, immunohistochemistry may serve as a practical surrogate. Recent tissue microarray studies suggested that PAX7 is a novel marker, because it was expressed consistently in Ewing sarcoma, in addition to rhabdomyosarcoma and synovial sarcoma. Here, we evaluated the utility of PAX7 immunohistochemistry in whole-tissue sections of an expanded array of round cell malignancies with adequate molecular characterisation. METHODS AND RESULTS: We stained 30 molecularly confirmed Ewing sarcomas, one EWSR1-NFATC2 sarcoma and 141 non-Ewing round cell tumours by a monoclonal antibody against PAX7. Staining was considered positive if at least 5% of tumour cells were stained. PAX7 was expressed in 27 of 30 Ewing sarcomas (90%), mainly in a diffuse and strong manner. Although NKX2-2 showed similar sensitivity, PAX7 showed more extensive and strong reactivity. One EWSR1-NFATC2 sarcoma co-expressed PAX7 and NKX2-2. PAX7 was also expressed in 24 of 141 non-Ewing tumours, including alveolar rhabdomyosarcomas (seven of 10), poorly differentiated synovial sarcomas (seven of 10), BCOR-CCNB3 sarcomas (eight of 10), small-cell osteosarcoma (one of five) and desmoplastic small round cell tumour (one of 10), one-third of which showed diffuse strong reactivity. CONCLUSIONS: Although we confirmed that PAX7 is a sensitive marker for Ewing sarcoma, anti-PAX7 antibody also stained several Ewing sarcoma mimics, whose spectrum was distinct from NKX2-2-positive non-Ewing entities. Further studies are required to determine how PAX7 could be integrated into practice to classify small round cell tumours efficiently.

Extraskeletal osteosarcoma: MDM2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity.

AIMS: Extraskeletal osteosarcoma (ESOS) is a sarcoma in the non-skeletal tissue that directly produces neoplastic osteoid or bone. De-differentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumour (MPNST) are the two most common types of sarcoma that can harbour heterologous osteosarcomatous differentiation. We aimed to determine the potential relationship of ESOS to DDLPS and MPNST. METHODS AND RESULTS: We investigated MDM2 and H3K27me3 status in 19 cases of ESOS, two of which contained a low-grade component. The ESOS affected deep soft tissues (n = 10), superficial soft tissues (n = 3) and organs (n = 6). Among 10 deep soft-tissue ESOS, six showed MDM2 amplification, four of which also harboured CDK4 co-amplification. Both ESOS with a low-grade component showed co-amplification for MDM2 and CDK4. Among the six organ-based ESOS three giant cell-rich ESOS showed an H3K27me3 deficiency (one in primary and two in metastatic sites). Using targeted next generation sequencing, an H3K27me3-deficient ESOS showed EED homozygous deletion, while none of the three showed alterations in NF1, CDKN2A or SUZ12 genes. During median follow-up of 20 months, all six patients with MDM2-amplified ESOS lived for 3-103 months, while two of the three patients with H3K27me3-deficient ESOS died from this disease in 4 and 20 months, respectively. CONCLUSION: We demonstrate that ESOS may include at least two small subsets: an MDM2-amplified deep soft-tissue ESOS (which may be related to DDLPS) and an H3K27me3-deficient organ-based ESOS (which is probably unrelated to MPNST). Larger studies are required to validate the present observations and investigate the clinical implications of such subcategorisation.

[Feasibility Study for Storage and Re-Utilization of Circulating Tumor Cells (CTCs)].

BACKGROUND: In this era of precision medicine, monitoring patients requires not only real time but also longitudinal sequence of samples at various time points. Based on this background, we focused on conditioned circumstances on fixation and storage for re-utilization of CTCs. MATERIALS: Instead of actual CTCs, Cell line (H1975) derived from lung cancer was used because of their scarceness of CTCs. METHODS: These cells were put on a slide by using an auto-smear device. The slides were evaluated under various centrifuge forces, fixations for the following storages. RESULTS AND DISCUSSION: The study indicated that 800 rpm for 1 min centrifuge and fixation by 95% ETOH was excellent. Further at least 5 cells per 1 mL cell solution were required for the following procedures including Fluorescence in situ hybridization (FISH) analysis. This study provides insights of new platform for evaluation of CTCs not only real time but also longitudinal sequence at various time points.

Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers.

The recent discovery and characterization of an oncogenic ROS1 gene fusion in a subset of lung cancers has raised significant clinical interest because small molecule inhibitors may be effective to these tumors. As lung cancers with ROS1 rearrangements comprise only 1-3% of lung adenocarcinomas, patients with such tumors must be identified to gain optimal benefit from molecular therapy. Recently, immunohistochemical analyses using a novel anti-ROS1 rabbit monoclonal antibody (D4D6) have shown promise for accurate identification of ROS1-rearranged cancers. To validate this finding, we compared the immunostaining results of tissue microarrays (TMAs) containing 17 ROS1-rearranged and 253 ROS1-non-rearranged lung carcinomas. All 17 ROS1-rearranged cancers showed ROS1 immunoreactivity mostly in a diffuse and moderate-to-strong manner with an H-score range of 5-300 (median, 260). In contrast, 69% of ROS1-non-rearranged cancers lacked detectable immunoreactivity, whereas the remaining 31% showed reactivity mainly in a weak or focal manner. The H-score for the entire ROS1-non-rearranged group ranged from 0 to 240 (median, 0). The difference in H-score between the two cohorts was statistically significant, and the H-score cutoff (≥150) allowed optimal discrimination (94% sensitivity and 98% specificity). Similar but slightly less-specific performance was achieved using the extent of diffuse (≥75%) staining or ≥2+ staining intensity as cutoffs. CD74-ROS1 and EZR-ROS1 fusions were significantly associated with at least focal globular immunoreactivity and plasma membranous accentuation, respectively, and these patterns were specific to ROS1-rearranged cases. Although full-length ROS1 is expressed in some ROS1-non-rearranged cases, we showed that establishment of an optimal set of interpretative criteria makes ROS1 immunohistochemistry a valuable method to rapidly and accurately screen lung cancer patients for appropriate molecular therapy.

Copy number loss of KDM5D may be a predictive biomarker for ATR inhibitor treatment in male patients with pulmonary squamous cell carcinoma.

A limited number of patients with lung squamous cell carcinoma (SCC) benefit clinically from molecular targeted drugs because of a lack of targetable driver alterations. We aimed to understand the prevalence and clinical significance of lysine-specific demethylase 5D (KDM5D) copy number loss in SCC and explore its potential as a predictive biomarker for ataxia-telangiectasia and Rad3-related (ATR) inhibitor treatment. We evaluated KDM5D copy number loss in 173 surgically resected SCCs from male patients using fluorescence in situ hybridization. KDM5D copy number loss was detected in 75 of the 173 patients (43%). Genome-wide expression profiles of the transcription start sites (TSSs) were obtained from 17 SCCs, for which the cap analysis of gene expression assay was performed, revealing that upregulated genes in tumors with the KDM5D copy number loss are associated with 'cell cycle', whereas downregulated genes in tumors with KDM5D copy number loss were associated with 'immune response'. Clinicopathologically, SCCs with KDM5D copy number loss were associated with late pathological stage (p = 0.0085) and high stromal content (p = 0.0254). Multiplexed fluorescent immunohistochemistry showed that the number of tumor-infiltrating CD8+ /T-bet+ T cells was lower in SCCs with KDM5D copy number loss than in wild-type tumors. In conclusion, approximately 40% of the male patients with SCC exhibited KDM5D copy number loss. Tumors in patients who show this distinct phenotype can be 'cold tumors', which are characterized by the paucity of tumor T-cell infiltration and usually do not respond to immunotherapy. Thus, they may be candidates for trials with ATR inhibitors.

Anaplastic lymphoma kinase status in rhabdomyosarcomas.

Rhabdomyosarcoma is a rare soft tissue sarcoma that typically affects children, adolescents, and young adults. Despite treatment via a multidisciplinary approach, the prognosis of advance-stage rhabdomyosarcomas remains poor, and a new treatment strategy is needed. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is a potential target for specific inhibitors. In this study, we investigated 116 rhabdomyosarcomas using a polymer-based ALK immunostaining method and correlated the results with clinicopathological parameters. In addition, we examined ALK status using dual-color fluorescence in situ hybridization, PCR, and sequencing. In immunohistochemical analysis, ALK was detected in 2 (6%) of 33 embryonal rhabdomyosarcomas, 42 (69%) of 61 alveolar rhabdomyosarcomas, and 0 (0%) of 22 other subtypes, including pleomorphic, adult-spindle-cell/sclerosing, and epithelioid variants. Compared with ALK-negative alveolar rhabdomyosarcomas, ALK-positive ones are presented with metastatic spread more frequently and showed a greater extent of myogenin reactivity. Overall survival was not associated with ALK expression. FOXO1 rearrangement was significantly associated with ALK immunoreactivity. The median ALK copy number was greater in ALK-positive tumors than in ALK-negative tumors. Most (93%) cases tested showed no selective increase in the ALK gene dosage. ALK selective amplification and low-level selective gain were noted in one and three cases, respectively. Further, a high-polysomy pattern (≥4 ALK copies in ≥40% of cells) was observed in seven cases. A significant increase in the ALK copy number was exclusive to the ALK-immunopositive cohort, but it was uncommon, accounting for only 30% of the 37 ALK-positive rhabdomyosarcomas. ALK gene rearrangement was not observed in either cohort, while an ALK somatic mutation (I1277T) was found in one ALK-negative embryonal case. Although it remains controversial whether ALK expression without gene rearrangement is therapeutically relevant, this comprehensive analysis may help future studies on the utility of ALK-targeted therapy for patients with rhabdomyosarcoma.

Novel NTRK3 Fusions in Fibrosarcomas of Adults.

NTRK fusions in malignant tumors are therapeutic targets of tyrosine kinase inhibitors. Because they occur only in a small subset of mesenchymal tumors, knowledge regarding the corresponding histology is important to effectively identify patients who could benefit from targeted therapy. In this study, using RNA sequencing, we identified novel NTRK3 fusions involving related partner genes in 2 adult bone and soft tissue tumors that met the current histologic criteria of fibrosarcoma. Case 1 involved the left radius of a 38-year-old woman, whereas in case 2, the right thigh of a 26-year-old man was affected. Histologically, both tumors consisted of the long fascicular growth of long spindle cells. The tumor in case 1 additionally showed focal myxoid changes. Tumor cells had nonpleomorphic, atypical nuclei, and lacked evidence of a specific line of differentiation. Both tumors showed widespread CD34 immunoreactivity and very limited expression of actin. RNA sequencing detected in-frame fusion transcripts of STRN (exon 3)-NTRK3 (exon 14) in case 1 and STRN3 (exon 3)-NTRK3 (exon 14) in case 2, which were confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. Pan-TRK immunostaining was diffusely positive in both cases. Fluorescence in situ hybridization showed signal patterns compatible with NTRK3 rearrangements in both cases, with case 2 additionally harboring a CDKN2A homozygous deletion. This study expands the clinicopathologic and genetic spectrum of sarcomas associated with NTRK fusions, and suggests that CD34-positive fibrosarcoma of bone and soft tissue could be a good candidate for NTRK testing.

Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion.

ATF1, CREB1, and CREM constitute the CREB family of transcription factors. The genes encoding these factors are involved in gene fusion events in human tumors. EWSR1-ATF1 and EWSR1-CREB1 are the 2 most characterized fusions, whereas EWSR1-CREM has been less studied. To better understand the phenotypic spectrum of mesenchymal tumors associated with the EWSR1-CREM fusion, we investigated archival cases using fluorescence in situ hybridization and/or RNA sequencing. Among 33 clear cell sarcomas of soft tissue tested, we found 1 specimen, a hand tumor bearing the rearrangements of EWSR1 and CREM, with classic histology and immunophenotype. None of 6 clear cell sarcoma-like tumors of the gastrointestinal tract tested harbored the EWSR1-CREM fusion. Among 11 angiomatoid fibrous histiocytomas, we found that 3 tumors of myxoid variant harbored the rearrangements of EWSR1 and CREM. All 3 tumors occurred in middle-aged men and involved the distal extremities (N=2) and the lung (N=1). Prominent lymphoid cuff, fibrous pseudocapsule, and amianthoid fiber were present in 3, 2, and 2 tumors, respectively, whereas none showed pseudoangiomatoid spaces. All 3 tumors were immunohistochemically positive for epithelial membrane antigen and desmin. These cases suggested a closer relationship between angiomatoid fibrous histiocytoma and a recently proposed novel group of myxoid tumors with CREB family fusions. Our cohort also included 2 unclassifiable sarcomas positive for EWSR1-CREM. One of these was an aggressive pediatric tumor of the abdominal cavity characterized by proliferation of swirling spindle cells immunopositive for cytokeratin and CD34. The other tumor derived from the chest wall of an adult and exhibited a MUC4-positive sclerosing epithelioid fibrosarcoma-like histology. Our study demonstrates that a wider phenotypic spectrum is associated with the EWSR1-CREM fusion than previously reported.

Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma.

Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present study aimed to explore the potential role of gene fusions in the tumorigenesis of poromas. RNA sequencing and reverse transcription PCR identified highly recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poromas (92/104 lesions, 88.5%) and their rare malignant counterpart, porocarcinomas (7/11 lesions, 63.6%). A WWTR1-NUTM1 fusion was identified in a single lesion of poroma. Fluorescent in-situ hybridization confirmed genomic rearrangements involving these genetic loci. Immunohistochemical staining could readily identify the YAP1 fusion products as nuclear expression of the N-terminal portion of YAP1 with a lack of the C-terminal portion. YAP1 and WWTR1, also known as YAP and TAZ, respectively, encode paralogous transcriptional activators of TEAD, which are negatively regulated by the Hippo signaling pathway. The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic roles. Our results demonstrate the frequent presence of transforming YAP1 fusions in poromas and porocarcinomas and suggest YAP1/TEAD-dependent transcription as a candidate therapeutic target against porocarcinoma.

Knowledge, attitude, and practice (KAP) of HIV prevention and HIV infection risks among Congolese refugees in Tanzania.

Little is known about HIV infection risks and risk behaviours of refugees living in resource-scarce post-emergency phase camps in Africa. Our study at Nyarugusu Camp in Tanzania, covering systematically selected refugees (n = 1140) and refugees living with HIV/AIDS (PLWHA) (n = 182), revealed that the level of HIV risk of systematically selected refugees increased after displacement, particularly regarding the number having transactional sex for money or gifts, while radio broadcast messages are perceived to promote a base of risk awareness within the refugee community. While condoms are yet to be widely used in the camp, some refugees having transactional sex tended to undertake their own health initiatives such as using a condom, under the influence of peer refugee health workers, particularly health information team (HIT) members. Nevertheless, PLWHA were less faithful to one partner and had more non-regular sexual partners than the HIV-negative group. Our study revealed that community-based outreach by refugee health workers is conducive to risk behaviour prevention in the post-emergency camp setting. It is recommended to increase the optimal use of "radio broadcast messages" and "HIT," which can act as agents to reach out to wider populations, and to strengthen the focus on safer sex education for PLWHA; the aim being to achieve dual risk reduction for both refugees living with and without HIV/AIDS.

Clarifying the Distinction Between Malignant Peripheral Nerve Sheath Tumor and Dedifferentiated Liposarcoma: A Critical Reappraisal of the Diagnostic Utility of MDM2 and H3K27me3 Status.

Malignant peripheral nerve sheath tumor (MPNST) and dedifferentiated liposarcoma (DDLPS) are 2 major types of pleomorphic spindle cell sarcoma. The differentiation of MPNST and DDLPS by histomorphology alone can be problematic. Although MDM2 amplification and PRC2 alteration leading to H3K27me3 deficiency are genetic hallmarks of DDLPS and MPNST, respectively, a small number of MDM2-amplified MPNSTs and H3K27me3-deficient DDLPSs have been reported in the literature. We systematically compared MDM2 and H3K27me3 status in 68 MPNSTs and 47 DDLPSs. Of the 62 MPNSTs, 22 were immunopositive for MDM2, mostly in a weak and/or focal manner. Of the 21 MDM2-positive MPNSTs successfully tested by fluorescence in situ hybridization, high-level MDM2 amplification was observed in 1 case. In contrast, MDM2 staining and high-level MDM2 amplification were positive in all the DDLPS tested (28/28 and 20/20). Of the 68 MPNSTs, 42 cases (62%) exhibited complete loss of H3K27me3. All the 13 MPNSTs that showed heterologous differentiation were deficient in H3K27me3. Of the 47 DDLPSs, 3 cases (6%) had complete loss of H3K27me3, all of which exhibited heterologous differentiation. One case of H3K27me3-deficient DDLPS exhibited homozygous loss of EED according to targeted next-generation sequencing, whereas there were no alterations in NF1 and CDKN2A. In conclusion, high-level MDM2 amplification strongly suggests DDLPS over MPNST. Although a good marker for MPNST, H3K27me3 deficiency also uncommonly occurs in DDLPS in association with PRC2 mutational inactivation. Because both markers are imperfectly specific, rare sarcomas with dual features could be encountered, and their classification should integrate other parameters.

The quality of life, mental health, and perceived stigma of leprosy patients in Bangladesh.

The present study aims to determine the quality of life (QOL) and general mental health of leprosy patients compared with the general population, and evaluate contributing factors such as socio-economic characteristics and perceived stigma. A total of 189 patients (160 outpatients, 29 inpatients) and 200 controls without leprosy or other chronic diseases were selected from Dhaka district, Bangladesh, using stratified random sampling. A Bangladeshi version of a structured questionnaire including socio-demographic characteristics-the Bangla version of the World Health Organization Quality of Life Assessment BREF (WHOQOL-BREF)-was used to assess QOL; a Self-Reporting Questionnaire (SRQ) was used to evaluate general mental health; the Barthel Index to control activities of daily living (ADL); and the authors' Perceived Stigma Questionnaire was used to assess perceived stigma of patients with leprosy. Medical records were examined to evaluate disability grades and impairment. QOL and general mental health scores of leprosy patients were worse than those of the general population. Multiple regression analysis revealed that factors potentially contributing to the deteriorated QOL of leprosy patients were the presence of perceived stigma, fewer years of education, the presence of deformities, and a lower annual income. Perceived stigma showed the greatest association with adverse QOL. We conclude that there is an urgent need for interventions sensitive to the effects of perceived stigma, gender, and medical conditions to improve the QOL and mental health of Bangladeshi leprosy patients.

Reaching hard-to-reach migrants by letters: an HIV/AIDS awareness programme in Nepal.

We assessed the impact of an HIV/AIDS programme for Nepalese migrants to India that involved writing letters. The programme created opportunities for sending HIV/AIDS-related messages to the migrants in India, and encouraging them practicing safer sex. Initially, they received the messages only from the programme, but later from their colleagues, spouses or other family members. They discussed the messages in groups, disseminated them, and sought more knowledge in their destinations. These findings indicated that using letters could be an effective way to reach inaccessible migrants at their destinations, and help them to improve their HIV/AIDS-related knowledge, and safer sex practices.

A challenge for monitoring iodine deficiency disorders in rural Nepal.

Developing a strategy for monitoring iodine deficiency disorders (IDD) remains a big challenge in rural Nepal where great variations could exist in IDD status. To explore the possibility of variation in urinary iodine excretion (UIE) level in rural settings, we carried out a detailed study of UIE among 586 school children of 20 schools in five villages. Our data revealed statisitically significant differences in UIE values among rural villages and schools in the same villages. The policy-makers should keep such variations in mind for a successful monitoring of IDD in Nepal and other countries where such variations may exist.

Mental health, quality of life, and nutritional status of adolescents in Dhaka, Bangladesh: comparison between an urban slum and a non-slum area.

This study aims to clarify the quality of life (QOL), mental health, and nutritional status of adolescents in Dhaka city, Bangladesh by comparing non-slum areas and slums, and to find the factors associated with their mental health problems. A sample of 187 boys and 137 girls from non-slum areas, and 157 boys and 121 girls from slums, between 11-18 years old were interviewed with a questionnaire consisting of a Bangla translation of the World Health Organization Quality of Life Assessment Instrument (WHOQOL-BREF), Self Reporting Questionnaire (SRQ), Youth Self-Report (YSR) and other questions. The height and weight of the respondents were measured. All significant differences in demographic characteristics, anthropometric measures, and WHOQOL-BREF were found to reflect worse conditions in slum than in non-slum areas. Contrarily, all differences in SRQ and YSR were worse in non-slum areas for both genders, except that the "conduct problems" score for YSR was worse for slum boys. Mental states were mainly associated with school enrollment and working status. Worse physical environment and QOL were found in slums, along with gender and area specific mental health difficulties. The results suggest gender specific needs and a requirement for area sensitive countermeasures.

Mathematical models assuming selective recruitment fitted to data for driver mortality and seat belt use in Japan.

Previous research has indicated that unbelted drivers are at higher risk of involvement in fatal crashes than belted drivers, suggesting selective recruitment that high-risk drivers are unlikely to become belt users. However, how the risk of involvement in fatal crashes among unbelted drivers varies according to the level of seat belt use among general drivers has yet to be clearly quantified. We, therefore, developed mathematical models describing the risk of fatal crashes in relation to seat belt use among the general public, and explored how these models fitted to changes in driver mortality and changes in observed seat belt use using Japanese data. Mortality data between 1979 and 1994 were obtained from vital statistics, and mortality data in the daytime and nighttime between 1980 and 2001 and belt use data between 1979 and 2001 were obtained from the National Police Agency. Regardless of the data set analyzed, exponential models, assuming that high-risk drivers would gradually become belt users in order of increasing risk as seat belt use among general motorists reached high levels, showed the best fit. Our models provide an insight into behavioral changes among high-risk drivers and support the selective recruitment hypothesis.

Relationship between mechanisms and activities at the time of pedestrian injury and activity limitation among school adolescents in Kathmandu, Nepal.

This study assessed the relationship between pedestrian activity at the time of injury, the type of vehicle involved and resulting activity limitation among school adolescents in the Kathmandu and Lalitpur districts of Nepal. A cross-sectional study of 1557 students in grades 6-8 across 14 schools was conducted using a self-administered questionnaire from August to September 2003. Twenty-three percent of adolescents reported pedestrian injuries, 38% were from urban and 21% from semi-urban areas. Adolescents were commonly injured by motorcycles and motor vehicles while crossing the road; however, while walking and playing, they were commonly injured by bicycles and motorcycles. Bicycles and motor vehicles were less likely to be involved in injury while crossing the roads and playing, respectively (p < 0.001). Activity was more likely to be limited for a longer period of time (> 7 days) with injuries endured while crossing the road (p < 0.001). In urban areas, boys and girls were more likely to be injured while crossing the road and walking, respectively (p < 0.05), and both were commonly injured by motorcycles. In semi-urban areas, boys and girls were commonly injured while walking and were more likely to be injured by motorcycles and bicycles, respectively (p < 0.05). In both areas, more boys than girls were injured while playing. These findings have important implications for pedestrian safety interventions in poor countries.