Levels and determinants of low birth weight in infants delivered under the national health insurance scheme in Northern Ghana.

This research determined the levels and odds ratios for low birth weight (LBW) infants delivered under the National Health Insurance Scheme (NHIS) compared to LBW infants delivered under the previous "Cash and Carry" system in Northern Ghana. Birth records of infants delivered before and after implementation of the NHIS in Northern Ghana were examined. Records of each day's births during the identified periods were abstracted. Days with fewer or no births were accommodated by oversampling from days before or after. Chi squared tests of independence were used to examine the bivariate association between categorical independent variables and LBW. Multiple logistic regression models were used to examine the relationships among selected variables for mothers and infants and the odds ratios for LBW. Infants delivered under NHIS had lower rates of LBW (16.8 %) compared to infants born under Cash and Carry (23.3 %). Mothers who delivered under NHIS were significantly less likely to have infants at LBW (unadjusted OR 0.65; 95 % CI 0.49, 0.86). The rate of LBW among infants delivered under NHIS is significantly lower than among infants delivered under Cash and Carry. The rate of LBW under Cash and Carry in 2000 fell by 27 % in relation to the NHIS in 2010. These findings confirm that the NHIS, which gives pregnant women in Northern Ghana four antenatal visits and access to skilled health professionals for delivery at no cost to the mother, significantly improved birth weight outcomes.

Mask wearing on an HBCU campus during the COVID-19 pandemic.

Objective: Young adults of age 18-29 years old account for the most COVID-19 cases in the US, and ethnic groups were affected disproportionately. Correctly wearing a face mask remains a critical intervention for COVID-19 mitigation. The study aimed to examine how well Historically Black Colleges and Universities (HBCUs) residents adhered to mask wearing during the pandemic. Methods: We conducted an observational study on an urban HBCU campus and the neighborhoods in Maryland for 13 weeks in spring 2021. Results: Of 1926 (1126 on campus; 800 off campus) persons observed, 89.8% wore masks, with 83.5% covering their mouths and noses. The HBCU campus showed better mask adherence than neighborhoods (92.0% vs. 86.7%). The most common improper mask wearing was nose out, followed by only-on-chin. Cloth and surgical masks were worn the most. Conclusion: The HBCU campus and neighborhood settings presented a high rate of facemask use during the pandemic.

A break-apart fluorescence in situ hybridization assay for detecting RET translocations in papillary thyroid carcinoma.

At least 15 different translocations have been described activating RET in papillary thyroid carcinomas. A break-apart fluorescence in situ hybridization (FISH) assay should detect many translocations involving the RET gene without requiring knowledge of the partner gene. G-banding and spectral karyotyping was performed to further characterize the papillary carcinoma cell line TPC-1. BAC clones flanking the 5' and 3' regions of RET were labeled with SpectrumRed and biotin detected with avidin-AMCA (blue). In addition to the previously described chromosomal t(1;10;21), TPC-1 was found to have del(7)(q22q31) and der(8)t(8;8)(p21;q11.2). With the BAC probes, TPC-1 interphase nuclei showed the expected signal pattern of one paired red-blue signal as well as separated red and blue signals from the rearranged RET gene in 93% of cells. Interphase nuclei from normal human lymphocytes showed two paired red-blue signals in 97% of cells. TPC-1 cells were found to have the previously described chromosomal rearrangement that involves chromosome 10, with few other cytogenetically detectable genomic alterations. RET rearrangement can be detected by a break-apart BAC FISH probe set in the interphase nuclei of TPC-1 cells. This assay can potentially detect clinically relevant translocations involving RET.

Chromosomal abnormalities of adenocarcinoma of the pancreas: identifying early and late changes.

The high level of karyotypic complexity found in epithelial neoplasms hinders the characterization of their cytogenetic evolution. Derivation of such pathways in adenocarcinoma of the pancreas has been particularly limited, because only a few pancreatic carcinomas are resected at an early stage of disease and so the number of primary carcinomas for which analysis of abnormal karyotypes has been reported is small. Here we report the clonal karyotypic abnormalities identified by G-banding analysis of 36 primary pancreatic carcinomas obtained from patients undergoing a Whipple resection with curative intent. The majority of the 36 carcinomas were diploid or triploid (33 of 36; 91%). Numerical alterations were found in all carcinomas for which a complete karyotype was determined. All the chromosomes were involved in gain, loss, or both gain and loss of the entire chromosome, in at least 8 and up to 28 of the carcinomas. Most commonly lost were chromosomes 18 (in 78% of the 36 carcinomas), 17 (56%), 6 (44%), 21 (42%), 22 (42%), Y (36%), and 4 (33%). Gain of chromosome 20 was observed in 10 of the 36 carcinomas. Structural abnormalities were common, resulting in partial chromosomal gains and losses, with a median number of 7 partial imbalances per carcinoma (range, 1-15). Sixteen carcinomas contained double-minute chromosomes, homogeneously staining regions, or both, indicating gene amplification. Pooling data for these 36 carcinomas with the primary carcinomas with karyotypes published in the Mitelman database (http://cgap.nci.nih.gov/Chromosomes/Mitelman), we defined pathways of karyotypic evolution. The most frequent chromosomal imbalances were -18 (67.6%), -10 (34.3%), -4 (31.4%), +20 (31.4%), -15p (23.8%), -14p (22.9%), +2 (21.9%), -5 (21.9%), -13p (20%), +16 (20%), -21p (19%), -17p (19%), +1q (19.0%). Recurrent imbalances identified as occurring early were -1p, -15p, -18, -7q, -8p, -17p, and -5; late recurrent imbalances were +11q, +7q, +6p, -19p, and +2. In contrast to reports from similar analyses in other epithelial carcinomas, we did not find evidence for multiple karyotypic evolutionary pathways.

None of Us Will Get Out of Here Alive: The Intersection of Perceived Risk for HIV, Risk Behaviors and Survival Expectations among African American Emerging Adults.

The Human Immunodeficiency Virus (HIV) significantly affects minority emerging adults, among whom the rate of new diagnoses is high and health disparities are more pronounced. Importantly, emerging adults today have limited knowledge of the earlier toll of the virus when it was identified as a killer. Among this population, perceptions of risk for HIV are low and sexual risk taking behaviors are high. The Get SMART Project is a behavioral intervention aimed to provide re-purposed HIV, alcohol, and substance abuse prevention education and HIV testing to African American emerging adults ages 18-24. The project was guided by the Health Belief Model, Community Promise, and Training for Institutional Procedures. Findings revealed that HIV testing is low. Marijuana and alcohol are drugs of choice. Emerging adults do not see themselves at risk for HIV, although they engaged in high-risk behaviors. Additionally, survival expectations influence behavior risk.

High mobility group protein I(Y): a candidate architectural protein for chromosomal rearrangements in prostate cancer cells.

The extent of chromosomal rearrangements correlates positively with the level of expression of the nuclear matrix high mobility group (HMG) proteins HMGI(Y) when tested in three human prostate cancer cell lines (PC-3 > DU-145 > LNCaP). HMGI(Y), topoisomerase II, and A-T-rich sequences have been reported to be located at the base of the DNA loop domains in both the nucleus and chromosome and are juxtapositioned for chromosomal rearrangement. Transfecting and expressing full-length HMG-I into the LNCaP cell markedly enhanced the presence and heterogeneity of unbalanced (nonreciprocal) chromosomal rearrangements but not of balanced rearrangements. Unbalanced chromosomal rearrangements are common in solid human tumors.

BCR/ABL rearrangement in two cases of Philadelphia chromosome negative chronic myeloid leukemia: deletion on the derivative chromosome 9 may or not be present.

The BCR/ABL gene rearrangement is the causing factor in chronic myeloid leukemia (CML). In most cases, it is cytogenetically visualized as a translocation between chromosomes 9 and 22, known as the Philadelphia (Ph) translocation. About 5-10% of CML patients lack cytogenetic evidence of the Ph translocation but show BCR/ABL fusion by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction. Deletions around the breakpoints on the derivative 9 including ABL and or BCR sequences occur in 10-15% of Ph+ CML patients and are thought to have prognostic significance. We describe two patients with CML and normal karyotype in whom cryptic rearrangements involving chromosomes 9 and 22 resulted in the causative BCR/ABL gene. FISH with a three-color probe combination revealed BCR/ABL fusion on chromosome 9 without deletion in one patient; the other patient had BCR/ABL on chromosome 22 with an associated derivative 9 deletion. We discuss the proposed mechanisms in the formation of BCR/ABL in the setting of a normal karyotype. Some authors reported that patients with the chimeric gene located on the derivative 9 have a poor clinical course. We suggest that deletion rather than location of the chimeric gene alone is more likely to be associated with prognosis.

Impact of prolonged infusions of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia.

The aromatic fatty acid sodium phenylbutyrate (PB) promotes cytostasis and differentiation in a wide variety of tumor types; among several molecular activities, inhibition of histone deacetylase (HDAC) may account for many of its pharmacodynamic effects. A Phase I study demonstrated promising preliminary evidence of clinical activity in acute myeloid leukemia and myelodysplastic syndrome; however, plasma concentrations achieved at the maximum tolerated dose were less than those targeted based on in vitro studies. Because prolonged exposure to suboptimal concentrations of PB in vitro led to pharmacodynamic changes similar to a more brief exposure to higher concentrations, a study of the feasibility of prolonged administration of sodium PB was performed. Selected patients with acute myeloid leukemia and myelodysplastic syndrome were treated with sodium PB as a continuous i.v. infusion via ambulatory infusion pump. Sequential cohorts were treated for 7 consecutive days out of 14 or with 21 consecutive days out of 28. Prolonged infusions were well tolerated; dose-limiting central nervous system toxicity developed in 1 of 23 patients treated. End-of-infusion plasma concentrations were maintained within a range sufficient to inhibit HDAC. Two patients on the 21/28 schedule developed hematological improvement. Prolonged infusions of PB are well tolerated making this an attractive platform for the clinical investigation of HDAC inhibition.

Clear cell sarcoma case report: complex karyotype including t(12;22) in primary and metastatic tumor.

Clear cell sarcoma (CCS) is a rare and aggressive tumor, arising mainly in the soft tissue of the extremities in young adults. A distinctive chromosomal translocation, t(12;22)(q13;q12), has been found in most reported cases. We performed cytogenetic analyses on a primary and subsequent metastatic CCS that contained the t(12;22), along with other complex karyotypic changes. G-banding chromosome analysis was supplemented by spectral karyotyping (SKY), a 24-color chromosome-paint FISH technique, thus allowing identification of three marker chromosomes, unbalanced translocations, and other complex abnormalities. Four of these involved additional copies and structural abnormalities of chromosome 8. Clarifying such secondary karyotypic changes in CCS may prove valuable to the understanding of tumor cell biology and clinical behavior.

Cytogenetic study of malignant triton tumor: a case report.

Malignant triton tumor (MTT) is a highly malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. Few cytogenetic studies of MTT have been reported using conventional cytogenetic analysis. Here, we report a comprehensive cytogenetic study of a case of MTT using G-banding, Spectral Karyotyping(), and fluorescence in situ hybridization (FISH) for specific regions. A complex hyperdiploid karyotype with multiple unbalanced translocations was observed: 48 approximately 55,XY,der(7)add(7)(p?)dup(7)[2],der(7) t(7;20)(p22;?)ins(20;19)[5],der(7)ins(8;7)(?;p22q36)t(3;8)t(8;20)[15],-8[5],-8[19],r(8)dup(8), +der(8)r(8;22)[4],-9[9],der(11)t(11;20)(p15;?)ins(20;19)[22],der(12)t(8;12)(q21;p13)[21],der(13) t(3;13)(q25;p11),-17,-19,der(19)t(17;19)(q11.2;q13.1),-20,-22,+4 approximately 7r[cp24]/46,XY[13]. The 1995 International System for Human Cytogenetic Nomenclature was followed where possible. Note that breakpoints were frequently omitted where only SKY information was known for a small part of an involved chromosome. Our analysis revealed some breakpoints in common with those previously reported in MTT, MPNST, and rhabdomyosarcoma, namely 7p22, 7q36, 11p15, 12p13, 13p11.2, 17q11.2, and 19q13.1. FISH showed high increase of copy number for MYC and loss of a single copy for TP53.

Health care access and utilization among ex-offenders in Baltimore: implications for policy.

The U.S. has the highest rate of incarceration in the world, releasing 12 million ex-offenders each year. These ex-offenders are disproportionately male, Black, poor, under-educated, and unhealthy, and return to our nation's poorest neighborhoods. Through a survey questionnaire and focus groups, this study examined the health status, health needs, access to and utilization of health care services among a sample of ex-offenders living in transitional housing in Baltimore City. More than half reported at least two major, chronic health problems. Only 40% had any form of health coverage; even more predictive of the ability to obtain health services was being able to name a specific provider (doctor, clinic or health organization). Recommendations for halting the downward spiral of poverty and sickness for this population and their communities include providing assistance with accessing, understanding, and navigating our complex and consumer-unfriendly health care system.

RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumors (IMTs) are rare soft tissue tumors occurring primarily in children and young adults. ALK gene rearrangements have been identified in this neoplasm, with fusion of the ALK gene at 2p23 to a number of different partner genes. Metaphase cytogenetic analyses of these tumors have been relatively few, however, and may help to identify additional variant partners. We report on an IMT from a 2-year-old boy with a karyotype of 45,XY,der(2)inv(2)(p23q12)del(2)(p11.1p11.2),-22. FISH showed ALK-RANBP2 fusion in this tumor. The breakpoint was cloned and the fusion was confirmed, making this the third reported case of IMT with ALK-RANBP2 fusion. In addition, we identified the ALK fusion partner in a previously reported IMT with t(2;17)(p23;q23) as CLTC, a gene reported to be involved in four other IMTs, and showed that the breakpoint involved a novel ALK-CLTC fusion. FISH evaluation of nine other IMTs identified CLTC as the fusion partner in one additional case, but RANBP2 was not involved in the remaining eight IMTs, suggesting that the variant partners involved in ALK rearrangements in IMTs are diverse.

Multicolor fluorescence in situ hybridization (SKY) in mycosis fungoides and Sézary syndrome: search for recurrent chromosome abnormalities.

Cutaneous T-cell lymphoma (CTCL) is a clonally derived lymphoproliferative disorder that preferentially involves the skin. The two major clinical expressions of CTCL, mycosis fungoides (MF) and Sézary syndrome (SS), have poorly understood pathogenesis. Chromosome abnormalities, mostly complex karyotypes, are seen in about 50% of patients with MF/SS, and there have only been a few instances of recurrent rearrangements. We analyzed 19 blood samples from patients with MF/SS with cytogenetics and multicolor FISH (SKY) to better describe the complex karyotypes and search for recurrent abnormalities or breakpoints. Comparison of phytohemagglutinin (PHA)-stimulated cultures versus a combination of interleukin 2 plus interleukin 7 showed similar efficiency in detecting abnormal clones; however, the PHA cultures yielded more analyzable metaphases. Nine of 19 patients (47%) had an abnormal karyotype. The most frequent abnormalities, in 7 of 9 cases, involved chromosome 10; followed by chromosome 6, in 6 of 9 cases; chromosomes 3, 7, 9, 17, and 19, in 5 of 9 cases; chromosomes 1 and 12, in 4 of 9 cases; and chromosomes 8, 11, and 13, in 3 of 9 cases. Most abnormalities were structural. Recurrent rearrangements included deleted chromosomes 6 and 13, in three cases each, and recurrent breakpoints at 1p32-36, 6q22-25, 17p11.2-13, 10q23-26, and 19p13.3, occurring in three or more cases. One patient had a pseudodicentric translocation between the short arms of chromosomes 8 and 17, confirmed by dual-color FISH and interpreted as psu dic(17;8)(p11.2;p11.2). Two patients with SS reported in the literature seem to have a similar translocation. If confirmed, a psu dic(17;8) could be the first recurring translocation detected in at least three patients with MF/SS.

Models for nutrition education to increase consumption of calcium and dairy products among African Americans.

Calcium and dairy consumption are documented to be low among African Americans and have demonstrated benefits to bone growth, overall nutritional status, and health throughout the life cycle. There is also an emerging relationship to the prevention of obesity. This low consumption has been attributed to both cultural and community/environmental barriers. Using a life course construct and an ecological model of health behavior, this paper will illustrate why nutrition education and food consumption behavior at one stage of the life cycle may influence health status at that stage as well as influence health and consumption of calcium and dairy products at subsequent stages. The life course construct recognizes that both past and present behavior and experiences (in this case food and nutrient intake) are shaped by the wider social, economic, and cultural context and therefore may provide clues to current patterns of health and disease. The ecological model, concerned with constructs of environmental change, behavior, and policies that may help people make choices in their daily life, complements the life course approach when examining the potential influence of nutrition education provided by federally funded food and nutrition programs on calcium and dairy consumption behavior across the life cycle. The "critical period model" within the life course construct is operative for calcium, a nutrient for which adequate intake is critically important during adolescence when peak bone density development, necessary for later protection against osteoporosis, is important.

Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors.

Imatinib has impressive activity against chronic myeloid leukaemia (CML), but does not appear to completely eradicate the disease. Although responses to interferon-alpha (IFN) are slower and less dramatic than those to imatinib, they can be durable even after discontinuation of the drug. Unlike imatinib, the specific mechanisms responsible for IFN's clinical activity in CML are unknown. We found that IFN induced a G1 cell cycle arrest, as well as terminal differentiation, of the CML cell line KT-1 and CML CD34+ cells from clinical specimens. Myeloid growth factors augmented the antileukaemic activity of IFN, and neutralising antibodies directed against myeloid growth factors inhibited IFN's antileukaemic activity. We next directly compared the effects of imatinib and IFN against differentiated and primitive CML progenitors from newly-diagnosed patients. Although less active against CML granulocyte-macrophage colony forming units than imatinib, IFN was significantly more toxic to primitive CML progenitors responsible for the maintenance of long-term cultures. Imatinib and IFN appear to have divergent effects on CML progenitors at different stages of maturation, with imatinib more active against differentiated CML progenitors and IFN more active against primitive CML progenitors. The different target cells for these agents may explain the disparities in the kinetics and durability of their clinical responses. At least part of the clinical effect of IFN in CML appears to result from its ability to differentiate primitive CML progenitors.

Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita.

Dyskeratosis congenita is a rare inherited disorder characterized by abnormal skin manifestations. Morbidity and mortality from this disease is usually due to bone marrow failure, but idiopathic pulmonary fibrosis and an increased cancer predisposition also occur. Families with autosomal dominant dyskeratosis congenita display anticipation and have mutations in the telomerase RNA gene. We identified a three-generation pedigree with autosomal dominant dyskeratosis congenita, anticipation, and telomere shortening. We show that a null mutation in motif D of the reverse transcriptase domain of the protein component of telomerase, hTERT, is associated with this phenotype. This mutation leads to haploinsufficiency of telomerase, and telomere shortening occurs despite the presence of telomerase. This finding emphasizes the importance of telomere maintenance and telomerase dosage for maintaining tissue proliferative capacity and has relevance for understanding mechanisms of age-related changes.

A de novo complex karyotype with two independent balanced translocations and a double inversion of chromosome 6 presenting with multiple congenital anomalies.

We report a 4-year-old female with a de novo complex karyotype with multiple chromosomal rearrangements and a distinctive phenotype. Her medical history is significant for having been a twin born at 35 weeks gestation, breech presentation, with feeding problems and poor growth as an infant, gastroesophageal reflux disease, peripheral pulmonic stenosis, omphalocele, high myopia, and severe mental retardation. She is small for her age with microcephaly, posteriorly sloping forehead, shallow orbits, long palpebral fissures, prominent nose, wide mouth, absent uvula, kyphosis, brachydactyly, bridged palmar crease, and hypertonia. Peripheral blood lymphocytes revealed a karyotype of 46,XX,t(1;12)(p22.3;q21.3),inv(6)(p24q23),t(7;18)(q11.2;q21.2) in all cells. Parental karyotypes and that of her twin were normal. Spectral Karyotyping (SKY) and fluorescence in situ hybridization (FISH) with whole chromosome paints for chromosomes 1, 6, 7, 12, and 18 did not reveal additional rearrangements. Prometaphase G-banding analysis suggested that the "inverted" chromosome 6 might contain a cryptic rearrangement. Although no deletion nor duplication was detected using metaphase comparative genomic hybridization (CGH), multicolor high resolution banding (mBAND) demonstrated a double inversion of chromosome 6, resulting in a final karyotype as above but including der(6)(pter --> p23::q21 --> q22.3::q21 --> p23::q22.3 --> qter).