'Whether it's your weapon or not, it's your home': US military spouse perspectives on personal firearm storage.

INTRODUCTION: In the USA, an estimated 45% of veterans personally own firearms. Firearm access increases the risk of suicide, so suicide prevention efforts in the US Department of Defense (DoD) focus on lethal means safety, including reducing firearm access. Spouse input may enhance effective messaging and intervention delivery of lethal means safety. This study used qualitative methods to explore the perspectives of military spouses or partners on personal firearm storage, including at-home decisions, on-base storage and existing messaging from the DoD. MATERIALS AND METHODS: Qualitative data were obtained using 1:1 interviews and focus groups with spouses/partners of US military service members (active duty, Reserve, National Guard, recently separated from the military) and representatives from military support organisations. Sessions focused on personal firearm storage (at home or on military installations) and military messaging around secure firearm storage and firearm suicide prevention. Data were analysed using a team-based, mixed deductive-inductive approach. RESULTS: Across 56 participants (August 2022-March 2023), the themes were variability in current home firearm storage and spousal participation in decision-making; uncertainty about firearm storage protocols on military installations; mixed awareness of secure firearm storage messaging from the military; and uncertainty about procedures or protocols for removing firearm access for an at-risk person. CONCLUSION: US military spouses are important messengers for firearm safety and suicide prevention, but they are currently underutilised. Tailored prevention campaigns should consider spousal dynamics and incorporate education about installation procedures.

A retrospective time trend study of firearm and non-firearm homicide in Cape Town from 1994 to 2013.

BACKGROUND: Gunshot injuries from interpersonal violence are a major cause of mortality. In South Africa (SA), the Firearms Control Act of 2000 sought to address firearm violence by removing illegally owned firearms from circulation, stricter regulation of legally owned firearms, and stricter licensing requirements. Over the last few years, varied implementation of the Act and police corruption have increased firearm availability. OBJECTIVES: To investigate whether changes in firearm availability in SA were associated with changes in firearm homicide rates. METHODS: This was a retrospective time trend study (1994 - 2013) using postmortem data. Time trends of firearm and non-firearm homicide rates were analysed with generalised linear models. Distinct time periods for temporal trends were assigned based on a priori assumptions regarding changes in the availability of firearms. RESULTS: Firearm and non-firearm homicide rates adjusted for age, sex and race exhibited different temporal trends. Non-firearm homicide rates either decreased or remained stable over the entire period. Firearm homicide increased at 13% annually from 1994 through 2000, and decreased by 15% from 2003 through 2006, corresponding with changes in firearm availability in 2001, 2003, 2007 and 2011. A 21% annual increase in firearm homicide after 2010 coincided with police fast-tracking new firearm licence applications. Cape Town's coloured population experienced a significantly greater increase than other population groups following additional exposure to illegal firearms from 2007. CONCLUSIONS: The strong association between firearm availability and homicide, and the reversal of a decreasing firearm homicide trend during a period of lax enforcement, provide further support for the association between reduced firearm homicide and stricter regulation.

Hepatitis D outbreak among children in a hepatitis B hyper-endemic settlement in Greenland.

Hepatitis B virus (HBV) infection is endemic in Greenland with 5-10% of the population being HBsAg-positive (chronic carriers). Surprisingly, despite of the high prevalence of HBV infection, acute and chronic hepatitis B, liver cirrhosis and primary hepatocellular carcinoma appear much less frequently than expected. The reasons for the low frequencies are unknown, but as a consequence implementation of a childhood HBV vaccination programme, though debated for years, has never been instituted. We describe an outbreak of hepatitis D (HDV) infection among children in a hepatitis B hyper-endemic settlement of 133 inhabitants on the west coast of Greenland. In 2006 a total of 27% of the inhabitants were HBsAg-positive (chronic carriers) and 83% were HBcAb-positive (previously exposed). Forty-six percent of the HBsAg-positive persons were below 20 years of age. On follow-up 1 year later a total of 68% of the HBsAg-positive persons were HDV-IgG positive. Five children, who were HBsAg-positive in 2006, had HDV-seroconverted from 2006 to 2007, indicating a HDV-super-infection. Most of the HDV-IgG positive children had markedly elevated liver enzymes. In the multivariate analysis, among the HBV and HDV markers, presence of HDV-IgG was most strongly associated with elevation of liver enzymes. In conclusion, the HBV-HDV super-infection and presumed HDV outbreak in this settlement challenges the notion that HBV infection may not be as harmless in Greenland as previously anticipated. The findings strongly suggest that HBV vaccination should be included in the child-immunization program in Greenland.

Human immunodeficiency virus type 1: drug resistance in treated and untreated Brazilian children.

Twenty-two vertically human immunodeficiency virus type 1 (HIV-1) infected Brazilian children were studied for antiretroviral drug resistance. They were separated into 2 groups according to the administration of antiretroviral therapy into those who presented disease symptoms or without symptoms and no therapy. Viral genome sequencing reactions were loaded on an automated DNA sampler (TruGene, Visible Genetics) and compared to a database of wild type HIV-1. In the former group 8 of 12 children presented isolates with mutations conferring resistance to protease inhibitors (PIs), 7 presented isolates resistant to nucleoside reverse transcriptase inhibitors (NRTIs) and 2 presented isolates resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten children were included in the antiretroviral na ve group. Eight were susceptible to NRTIs and all of them were susceptible to PIs; one presented the V108I mutation, which confers low-level resistance to NNRTIs. The data report HIV mutant isolates both in treated and untreated infants. However, the frequency and the level of drug resistance were more frequent in the group receiving antiretroviral therapy, corroborating the concept of selective pressure acting on the emergence of resistant viral strains. The children who presented alterations at polymorphism sites should be monitored for the development of additional mutations occurring at relevant resistance codons.

Human immunodeficiency virus type 1: drug resistance in treated and untreated Brazilian children

Twenty-two vertically human immunodeficiency virus type 1 (HIV-1) infected Brazilian children were studied for antiretroviral drug resistance. They were separated into 2 groups according to the administration of antiretroviral therapy into those who presented disease symptoms or without symptoms and no therapy. Viral genome sequencing reactions were loaded on an automated DNA sampler (TruGene, Visible Genetics) and compared to a database of wild type HIV-1. In the former group 8 of 12 children presented isolates with mutations conferring resistance to protease inhibitors (PIs), 7 presented isolates resistant to nucleoside reverse transcriptase inhibitors (NRTIs) and 2 presented isolates resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten children were included in the antiretroviral naﶥ group. Eight were susceptible to NRTIs and all of them were susceptible to PIs; one presented the V108I mutation, which confers low-level resistance to NNRTIs. The data report HIV mutant isolates both in treated and untreated infants. However, the frequency and the level of drug resistance were more frequent in the group receiving antiretroviral therapy, corroborating the concept of selective pressure acting on the emergence of resistant viral strains. The children who presented alterations at polymorphism sites should be monitored for the development of additional mutations occurring at relevant resistance codons

Virus da Imunodeficiencia Humana: considerações gerais sobre a especificidade e sensibilidade de metodos laboratoriais para a detecção de anticorpos e antigenos especificos / Human immunodeficiency virus: general aspects concerning laboratorial methods specificity and sensitivity to detect specific antigens and antibodies

O diagnostico laboratorial da infeccao pelo virus da imunodeficiencia humana tipo 1 pode ser feito mediante a aplicacao de testes sorologicos de terceira geracao. Reatividade inespecificas podem, entretanto, ser observadas em diferentess grupos populacionais, para a deteccao de anticorpos contra HIV por metodos imunoenzimaticos, conforme observado na analise de amostras sorologicas de gestantes (3,9 porcento), hepatopatas (3,0 porcento) e populacao pediatrica (1,03 porcento). Os valores de inespecificidade reforcam o conceito de que a deteccao de anticorpos contra HIV deve ser feita pela analise e interpretacao de, ao menos, dois testes de diferentes procedencias, em uma primeira coleta. Metodos de triagem de quarta geracao, que permitem a deteccao simultanea de anticorpos e antigeno p24 do HIV, apresentam sensibilidade comparavel a das metodologias tradicionais, sendo de particular valor no diagnostico precoce da infeccao. Diferentes amostras de sangue de tres pacientes, coletadas em periodos distintos, foram analisadas comparativamente por testes imunoenzimaticos de terceira geracao (Cobas, Axsym e Ortho) e quarta geracao (ELFA HIV DUO). Os resultados demonstram a possibilidade de antecipar a deteccao dos marcadores da infeccao viral em periodos que podem variar de quatro a 12 dias, quando comparados a metodos de terceira geracao, que detectam apenas anticorpos

Detection of hepatitis B virus antigens in paraffin-embedded liver specimens from the Amazon region, Brazil.

Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period from 1934 to 1967, were analyzed by immunohistochemical assays to detect hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material belongs to the Yellow Fever Collection, Department of Pathology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time according to clinical aspects and histopathological findings reporting viral hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79 specimens, 69 were collected at the Labrea Region and the other 10 in difFerent other localities in the Amazon Region. The five micra thick histological slices were analyzed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) by immunoperoxidase technique. An immunofluorescence assay was applied to the detection of hepatitis D, yellow fever and dengue virus antigens. Nine (11.4%) histological samples were HBsAg reactive and 5 (6.3%) were HBcAg reactive. The oldest reactive sample was from 1934. Viral antigens related to the other pathologies were not detected in this study. Our results confirm that the methodology described may be used to elucidate the aetiology of hepatitis diseases even after a long time of conservation of the specimens.

Detection of hepatitis B virus antigens in paraffin-embedded liver specimens from the Amazon Region, Brazil

Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period from 1934 to 1967, were analyzed by immunohistochemical assays to detect hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material belongs to the Yellow Fever Collection, Department of Pathology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time according to clinical aspects and histopathological findings reporting viral hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79 specimens, 69 were collected at the Labrea Region and the other 10 in different other localities in the Amazon Region. The five micra thick histological slices were analyzed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) by immunoperoxidase technique. An immunofluorescence assay was applied to the detection of hepatitis D, yellow fever and dengue virus antigens. Nine (11.4 percent) histological samples were HBsAg reactive and 5 (6.3 percent) were HBcAg reactive. The oldest reactive sample was from 1934. Viral antigens related to the other pathologies were not detected in this study. Our results confirm that the methodology described may be used to elucidate the aetiology of hepatitis diseases even after a long time of conservation of the specimens

Effects of p,p'-DDE on immature cells in culture at concentrations relevant to the Alaskan environment.

Arctic Alaskan Natives who maintain a traditional lifestyle have a disease profile that is significantly different from the general US population. There is concern that food sources containing environmental pollutants may contribute to this profile. In a preliminary study, umbilical cord blood was examined for the presence of several environmental contaminants. All cord blood samples analyzed thus far contain p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) with an average concentration of 0.33 microg/l. This study was undertaken to ascertain if this concentration of p,p'-DDE had detectable effects on immature cells in culture. NIH 3T3 (embryonic mouse fibroblast) and WS1 (human fetal fibroblast) cultures were exposed to media containing either 1 or 10 times the average cord blood concentration of p,p'-DDE. Initial experiments indicated that exposure to p,p'-DDE resulted in a decrease in the cell number of both cell types. Subsequent analysis revealed that the decrease in cell number was due to cell death in NIH 3T3 cells and to cell-cycle arrest in WS1 cells. Furthermore, p,p'-DDE decreased the long-term survival of NIH 3T3 but not WS1 cells. This study has demonstrated that p,p'-DDE, at relevant environmental concentrations, has significant effects on two immature mammalian cell types in culture. In addition, these results highlight the necessity for further studies to address the specific effects of p,p'-DDE on developing fetal systems.

Identification of mismatch repair protein complexes in HeLa nuclear extracts and their interaction with heteroduplex DNA.

Deficiencies in DNA mismatch repair (MMR) have been found in hereditary colon cancers (hereditary non-polyposis colon cancer, HNPCC) as well as in sporadic cancers, illustrating the importance of MMR in maintaining genomic integrity. We have examined the interactions of specific mismatch repair proteins in human nuclear extracts. Western blot and co-immunoprecipitation studies indicate two complexes as follows: one consisting of hMSH2, hMSH6, hMLH1, and hPMS2 and the other consisting of hMSH2, hMSH6, hMLH1, and hPMS1. These interactions occur without the addition of ATP. Furthermore, the protein complexes specifically bind to mismatched DNA and not to a similar homoduplex oligonucleotide. The protein complex-DNA interactions occur primarily through hMSH6, although hMSH2 can also become cross-linked to the mismatched substrate when not participating in the MMR protein complex. In the presence of ATP the binding of hMSH6 to mismatched DNA is decreased. In addition, hMLH1, hPMS2, and hPMS1 no longer interact with each other or with the hMutSalpha complex (hMSH2 and hMSH6). However, the ability of hMLH1 to co-immunoprecipitate mismatched DNA increases in the presence of ATP. This interaction is dependent on the presence of the mismatch and does not appear to involve a direct binding of hMLH1 to the DNA.

Inefficient in vivo repair of mismatches at an oncogenic hotspot correlated with lack of binding by mismatch repair proteins and with phase of the cell cycle.

Repair rates of mismatched nucleotides located at an activating hotspot of mutation, H-ras codon 12, have been analyzed in vivo in mammalian cells. Repair rates at codon 12 are significantly improved in cells synchronized to the G(1) stage of the mammalian cell cycle as compared with non-synchronous cells, demonstrating that mismatch repair mechanisms are active in G(1). Repair rates in non-synchronous cells for the same mismatches at a nearby non-hotspot of mutation, H-ras codon 10, are also significantly improved over repair rates at codon 12 in non-synchronous cells, demonstrating that DNA mismatch repair rates can differ depending on the sequence context. These results suggest that inefficiencies in mismatch repair are responsible, at least in part, for the well documented hotspot of mutation at codon 12. Further experiments involving gel-shift analysis demonstrate a mismatch-specific binding factor for which the degree of binding correlates with in vivo repair rates for each mismatch tested at the codon 12 location. This binding factor appears to be the hMutSalpha heterodimer as identified by monoclonal antibody assay and inhibition of binding by ATP. Furthermore, a lack of binding is observed only for G:A mismatches at the codon 12 location. This lack of binding correlates with the low rate of repair observed in vivo for G:A mismatches at codon 12 versus the improved repair rates for G:A mismatches at codon 10. This may have biological relevance in that G:C-->T:A tranversions are a common mutation at this location in naturally occurring human tumors. These results suggest that there is lowered efficiency in the kinetics of mismatch repair at codon 12. Mismatches at this location are therefore more likely to be replicated before repair, thus resulting in a mutation.

[Clinical, laboratory and liver histology of HBsAg-positive volunteer blood donors in Belo Horizonte, State of Minas Gerais, Brazil]. / Estudo clínico, laboratorial e da histologia hepática de candidatos a doadores de sangue HBsAg positivos em Belo Horizonte.

Two hundred and fifty two blood donors HBsAg positive (mean age = 32.6, 91, 7% male) were searched into a transversal study to determine their clinical, laboratorial and histological characteristics. It was also compared the positiviness and negativiness of the serologic markers HBeAg, anti-Hbe and IgM anti-HBc with the values of serum aminotransferases. Hepatomegaly and splenomegaly were detected in 9.9% (25/252) and in 2.4% (6/252) respectively. In 17.5% (44/251) and 28.3% (71/251) the AST and ALT were respectively, over 50 UI/I. The positive frequencies of the various serologic markers of hepatitis B virus in 120 patients were: anti-HBc total in 89.5% (102/114), HBeAg in 25.7% (28/109) anti-Hbe in 67.3% (66/98), IgM anti-HBc in 40.8% (49/120); anti-Delta in 0.0% (0.66). Thirty one patients were submitted to liver biopsy, due do clinical alteration and/or of the aminotransferases. The hystological findings were: normal liver in 16.1% (5/31), non specific hystological alterations in 22.6% (7/31), persistent chronic hepatitis in 22.6% (7/31), active chronic hepatitis in 6.5% (2/31), cirrhosis in 12.9% (4/31), alcoholic hepatitis in 3.2% (1/31), lobular chronic hepatitis in 3.2% (1/31) and alterations exclusively due to schistosomiasis in 12.9% (4/31). Schistosomiasis elements (granuloma and/or Symmers fibrosis) were also notived in 7 patients. The comparative analysis of positiveness and negativeness of the serologic markers with the aminotransferases ("t" test of Student) showed significative difference of the averages (p < 0.05) only in relation to the simultaneous positeveness and negativeness of the HBeAg and IgM anti-HBc (average of AST = 56.11 and ALT = 78.00 when HBeAg and IgM anti-HBc were positive; average of AST = 24.25 and ALT = 27.00 when HBeAg and IgM anti-HBc were negative). According to this study the conclusion are: 1) The presence of two markers (HBeAg and IgM anti-HBc) and not only one determinant of viral replication in asymptomatic HBsAg carriers can strongly indicate a significant biochemical activity suggestive of hepatocellular lesion. 2) The presence of HBeAg in 25.7% (28/109) clearly shows the high rate of carriers with a potential of infectivity. 3) The results of hepatic histology shows that the majority of our patients had either normal liver or mild histological alterations. It is important to notice that only the cases with elevated aminotransferases were submitted to liver biopsies. The alterations caused by schistosomiasis shows, as is well known, the high prevalence of the parasitism in our surroundings. 4) The clinical aspects of the patients studied did not show significant alterations. Risk factors to get the infection were low. The hematologic and biochemical parameters (except aminotransferases) were either normal or just slightly abnormal. It was not detected a statistically significant difference. 5) The co-infections by delta virus was null.

Site- and strand-specific mismatch repair of human H-ras genomic DNA in a mammalian cell line.

Defective mismatch repair has recently been implicated as the major contributor towards the mutator phenotype observed in tumour cell lines derived from patients diagnosed with hereditary non-polyposis colon cancer (HNPCC). Cell lines from other cancer-prone syndromes, such as xeroderma pigmentosum, have been found to be defective in nucleotide excision repair of damaged bases. Some genetic complementation groups are defective specifically in transcription-coupled excision repair, although this type of repair defect has not been associated with cancer proneness. Mechanisms contributing to the high incidence of activating point mutations in oncogenes (such as H-ras codon 12) are not understood. It is possible that novel mechanisms of misrepair or misreplication occur at these sites in addition to the above DNA repair mechanisms. In this study, we have compared the rate of strand-directed mismatch repair of four mispairs (G:A, A:C, T:C and G:T) at the H-ras codon 12, middle G:C position. Our results indicate that, although this location is not a 'hot spot' for bacterial mismatch repair, it is a 'hot spot' for decreased repair of specific mismatched bases within NIH 3T3 cells. NIH 3T3, unlike Escherichia coli, have an extremely low repair rate of the G:A mispair (35%), as well as the A:C mispair (58%) at this location. NIH 3T3 also have a moderately low repair rate of the T:C mispair (80%) at the codon 12 location. Conversely, NIH 3T3 repair of G:T (100%) is comparable to E. coli repair (94%) of this mismatch. These results demonstrate that a mismatch containing an incorrect adenine on either strand at the H-ras codon 12 middle base pair location is most likely to undergo a mutational event in NIH 3T3 cells. Conversely, a mismatch containing an incorrect thymine in the transcribed strand is least likely to undergo a mutational event.

Unbalanced translocation t(5;17) in an typical acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL; M3 in the FAB classification) is specifically associated with the t(15;17)(q23;q12) and the consequent formation of a PML/RARA fusion gene. A few cases of APL with a t(11;17)(q23;q12) and a PLZF/RARA fusion gene have recently been reported. In addition, a new variant, t(5;17)(q32;q12), with a RARA rearrangement was described in a child with atypical APL. We report an unbalanced der(5)t(5;17) in an atypical APL case showing unusual dysgranulopoiesis and some M2 features. The breakpoints were difficult to localize precisely on chromosome 5, because the translocation may have occurred on a previous del(5q). The karyotype also showed del(8q) and multiple double-minutes (dmin). Molecular studies evidenced RARA rearrangement but showed neither PML rearrangement nor PML/RARA fusion. Fluorescence in situ hybridization revealed that the dmin were of chromosome 8 origin and that they accounted for the MYC amplification observed in Southern blots. The patient did very poorly despite chemotherapy and all-trans retinoic acid (ATRA) treatment. Thus, the t(5;17) could represent a second type of variant translocation in APL that, like the disease associated with t(11;17), does not seem to respond to ATRA therapy. Whereas RARA rearrangement appears sufficient for an APL-like phenotype, it seems that the presence of a classical PML/RARA is required for typical APL with response to ATRA.

Translocation of BCR to chromosome 9 in a Philadelphia-negative chronic myeloid leukemia.

We report the case of a patient having Philadelphia-negative, bcr-abl-positive chronic myeloid leukemia. In situ hybridization showed the presence of the bcr-abl fusion on the chromosome 9 long arm in all mitoses observed. Stability of the disease was very difficult to obtain because of serious adverse effects to interferon and chemotherapy, mainly grade IV neutropenia, and a blast crisis occurred 12 months after diagnosis. Only three other patients with such presentation (Philadelphia negative, bcr-abl positive with bcr-abl fusion on the chromosome 9 long arm) have been reported, with a poor therapeutic response and outcome in two of them. Translocation of BCR to chromosome 9 may therefore have a worse prognosis than translocation of ABL to chromosome 22 in Philadelphia-negative chronic myeloid leukemia.

Direct evidence for dissociated megakaryocytic chimaerism in a Wiskott-Aldrich patient successfully allografted.

We report a Wiskott-Aldrich patient who underwent allogeneic bone marrow transplantation from his HLA-identical sister at the age of 25. Conditioning regimen consisted of cyclophosphamide (180 mg/kg) and thoraco-abdominal irradiation (6 Grays). Cytogenetic follow-up revealed rapid and complete lymphoid chimaerism, but prolonged mixed bone marrow chimaerism. Correlative interphase cytogenetics performed on bone marrow smears using dual-colour fluorescence in situ hybridization with X and Y specific probes showed that the proportion of donor cells was significantly higher within megakaryocytes than in other lineages. This patient therefore presented with dissociated lineage engraftment, which is not exceptional in congenital diseases and aplastic anaemia, but has not previously been described in Wiskott-Aldrich syndrome. Bone marrow transplantation was successful despite this delayed engraftment which ensured adequate production in the involved cell lines.

Acute promyelocytic leukemia cases with nonreciprocal PML/RARa or RARa/PML fusion genes.

Tumor-associated chromosome translocations usually lead to the formation of two reciprocal fusion genes: one thought to be involved in the transformation process, the other the mechanical consequence of the translocation event. In the case of acute promyelocytic leukemia (APL) blasts, the 15;17 chromosome translocation generates the putatively transforming PML/RARa fusion gene and its reciprocal RARa/PML. We report APL cases with submicroscopic 15;17 recombinations leading to the formation of nonreciprocal PML/RARa or RARa/PML fusion genes. Therefore, each of the two reciprocal translocation products may be independently formed and selected by the leukemic phenotype, implying that both are involved in tumorigenesis.