Prevalence and Determinants of Chronic Obstructive Pulmonary Disease (COPD) in Bangladesh

Rationale: There is a paucity of population-based data on COPD prevalence and its determinants in Bangladesh.

Objective: To measure COPD prevalence and socioeconomic and lifestyle determinants among ≥40 years Bangladeshi adults.

Methods: In a cross-sectional study, we measured lung function of 3744 randomly selected adults ≥40 years from rural and urban areas in Bangladesh, using a handheld spirometer. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1^st second (FEV₁) to Forced Vital Capacity (FVC) <?0.7. In addition, COPD was also assessed by the lower limit of normal (LLN) threshold defined as lower fifth percentile for the predicted FEV₁/FVC.

Results: The prevalence of COPD was 13.5% by GOLD criteria and 10.3% by LLN criteria. Prevalence of COPD was higher among rural than urban residents and in males than females. More than half of the COPD cases were stage II COPD by both criteria. Milder cases (Stages I and II) were over estimated by the GOLD fixed criteria, but more severe cases (Stages III and IV) were similarly classified. In multiple logistic regression analysis, older age, male sex, illiteracy, underweight, history of smoking (both current and former), history of asthma and solid fuel use were significant predictors of COPD.

Conclusion: COPD is a highly prevalent and grossly underdiagnosed public health problem in Bangladeshi adults aged 40 years or older. Illiteracy, smoking and biomass fuel burning are modifiable determinants of COPD.     

Dense IgG4 plasma cell infiltrates associated with chronic infectious aortitis: implications for the diagnosis of IgG4-related disease

BackgroundIgG4-related aortitis is a newly recognized form of noninfectious aortitis that occurs as part of the spectrum of a systemic disease referred to as IgG4-related disease. IgG4-related aortitis is distinguished from giant cell aortitis and Takayasu aortitis in part by the presence of increased numbers of IgG4-expressing plasma cells. Chronic infectious aortitis can also display lymphoplasmacytic infiltrates, but the degree of IgG4 expression in these cases has not been specifically evaluated.MethodsTwo cases of chronic active infectious abdominal aortitis were prospectively identified. Both were due to gram-positive bacteria, and at least one of the cases was due to chronic active Staphylococcus aureus infection. The degree of IgG4 plasma cell infiltration was assessed by immunohistochemistry.ResultsBoth cases of chronic infectious aortitis focally displayed high levels of IgG4-expressing plasma cells, greater than 50% of the IgG-expressing plasma cells, and greater than 50 IgG4-expressing plasma cells per high-power field.ConclusionsFocal dense IgG4 plasma cell infiltrates can be seen in association with chronic infectious aortitis due to gram-positive bacteria, including Staphylococcus aureus. This observation supports the proposal that chronic Staphylococcus aureus infection may stimulate a Th2-mediated elevation in IgG4. The pathologic diagnosis of IgG4-related aortitis should not be based solely on the presence of increased IgG4 plasma cell counts from immunohistochemistry, but requires consideration of the overall pathology, including careful exclusion of infectious aortitis.     

A case series of shared delusional infestation: folie à deux revisited

Delusional infestation describes the unshakeable belief that one's skin is infected or infested with an external organism or inanimate material, in the absence of supportive medical evidence. It is one of the most challenging psychodermatological conditions to manage, given the rigidity of patients’ physically focused health beliefs, and the competing need to introduce antipsychotic therapy to bring about resolution. This is rendered exponentially more complex when partners or family members are similarly afflicted. This situation is known as shared delusional infestation, shared psychotic disorder (SPD), or folie à deux. We present a series of three couples with SPD who were referred to our tertiary psychodermatology service during the same year. On examining the literature we were intrigued to discover that subtly different subtypes of SPD have been recognized since the late 1800s. These include folie simultanée, imposée, communiquée and induite. Our cases neatly demonstrate three of these variants, and highlight the difficulties in facilitating effective treatment.     

Friction Stir Welding of Thick Plates of 4Y3Gd Mg Alloy: An Investigation of Microstructure and Mechanical Properties

Applications of non-ferrous light metal alloys are especially popular in the field of aerospace. Hence it is important to investigate their properties in joining processes such as welding. Solid state joining process such as friction stir welding (FSW) is quite efficient for joining non-ferrous alloys, but with thick plates, challenges increase. In this study, Mg alloy plates of thickness 11.5 mm were successfully welded via single-pass FSW. Due to the dynamic recrystallization, grain size in the stir zone was reduced to 16 µm which is ≈15 times smaller than the parent material. The optimized rotational speed and traverse speed for optimum weld integrity were found to be 710 rpm and 100 mm/min, respectively. A sound weld with 98.96% joint efficiency, having an Ultimate Tensile Strength (UTS) of 161.8 MPa and elongation of 27.83%, was accomplished. Microhardness of the nugget was increased by 14.3%.     

Mice with cardiomyocyte-specific disruption of the endothelin-1 gene are resistant to hyperthyroid cardiac hypertrophy

Endothelin 1 (ET-1), a potent vasoconstrictor peptide expressed by endothelium, is also produced in the heart in response to a variety of stresses. It induces hypertrophy in cultured cardiac myocytes but only at concentrations far greater than those found in plasma. We tested whether ET-1 generated by cardiac myocytes in vivo is a local signal for cardiac hypertrophy. To avoid the perinatal lethality seen in systemic ET-1-null mice, we used the Cre/loxP system to generate mice with cardiac myocyte-specific disruption of the ET-1 gene. We used the alpha-myosin heavy chain promoter to drive expression of Cre and were able to obtain 75% reduction in ET-1 mRNA in cardiac myocytes isolated from these mice at baseline and after stimulation, in vivo, for 24 h with tri-iodothyronine (T3). Necropsy measurements of cardiac mass indexed for body weight showed a 57% reduction in cardiac hypertrophy in response to 16 days of exogenous T3 in mice homozygous for the disrupted ET-1 allele compared to siblings with an intact ET-1 gene. Moreover, in vivo MRI showed only a 3% increase in left ventricular mass indexed for body weight in mice with the disrupted allele after 3 weeks of T3 treatment versus a 27% increase in mice with an intact ET-1 gene. A reduced hypertrophic response was confirmed by planimetry of cardiac myocytes. We conclude that ET-1, produced locally by cardiac myocytes, and acting in a paracrine/autocrine manner, is an important signal for myocardial hypertrophy that facilitates the response to thyroid hormone.     

Protein Kinase CK1αLS Promotes Vascular Cell Proliferation and Intimal Hyperplasia

Protein kinase CK1α regulates several fundamental cellular processes including proliferation and differentiation. Up to four forms of this kinase are expressed in vertebrates resulting from alternative splicing of exons; these exons encode either the L-insert located within the catalytic domain or the S-insert located at the C terminus of the protein. Whereas the L-insert is known to target the kinase to the nucleus, the functional significance of nuclear CK1αLS has been unclear. Here we demonstrate that selective L-insert-targeted short hairpin small interfering RNA-mediated knockdown of CK1αLS in human vascular endothelial cells and vascular smooth muscle cells impairs proliferation and abolishes hydrogen peroxide-stimulated proliferation of vascular smooth muscle cells, with the cells accumulating in G₀/G₁. In addition, selective knockdown of CK1αLS in cultured human arteries inhibits vascular activation, preventing smooth muscle cell proliferation, intimal hyperplasia, and proteoglycan deposition. Knockdown of CK1αLS results in the harmonious down-regulation of its target substrate heterogeneous nuclear ribonucleoprotein C and results in the altered expression or alternative splicing of key genes involved in cellular activation including CXCR4, MMP3, CSF2, and SMURF1. Our results indicate that the nuclear form of CK1α in humans, CK1αLS, plays a critical role in vascular cell proliferation, cellular activation, and hydrogen peroxide-mediated mitogenic signal transduction.A key morphological distinction between vertebrates and invertebrates is the presence of a closed endothelial-lined vascular system in the vertebrates.¹ Activation of the cells comprising the vertebrate vasculature results in cellular proliferation, enhanced proteoglycan deposition, and secretion of growth factors and cytokines.^2,3,4 Such vascular activation is an important process in both vascular development and in vascular diseases such as atherosclerosis and postangioplasty restenosis. Thus, an understanding of the vertebrate-specific signaling pathways regulating vascular cell activation is of high importance.Protein kinase CK1α regulates several fundamental cellular processes including proliferation and differentiation.⁵ Up to four different forms of the kinase exist owing to the alternative splicing of exons encoding either the L-insert located within the catalytic domain or the S-insert located at the C terminus of the protein.^6,7,8,9 Protein kinase CK1α itself is highly conserved among all metazoans. However, the exon encoding the nuclear localizing L-insert is restricted to vertebrates.¹⁰ Whereas vertebrates may contain up to four different splice forms of CK1α, humans are thought to only express three forms: CK1α, CK1αS, and CK1αLS, which are also referred to as CK1α1, CK1α2, and CK1α3, respectively. In the nucleus, CK1αLS probably plays a role in pre-mRNA processing and alternative splicing based on its ability to phosphorylate the highly abundant vertebrate-specific pre-mRNA binding protein heterogeneous nuclear ribonucleoprotein C (hnRNP-C)^10,11,12 and its localization to nuclear speckles,⁶ sites of accumulation of pre-mRNA processing factors.Within the vessel wall, hydrogen peroxide (H₂O₂) plays important roles in mediating vascular activation resulting from diverse stimuli including altered flow, growth factors, cytokines, and vascular injury.^13,14 In fact, vertebrate cells are known to proliferate in response to low concentrations of H₂O₂.¹⁵ Low levels of H₂O₂ are generated by vertebrate cells in response to growth factor-mediated signaling, and this mitogenic H₂O₂ activates CK1αLS, which then phosphorylates hnRNP-C.^10,11 It is known that hnRNP-C modulates the expression of several genes regulating cell growth and survival, including platelet-derived growth factor B chain (PDGF-B),¹⁶ c-myc,¹⁷ p53,¹⁸ the X-chromosome-linked inhibitor of apoptosis,¹⁹ and the urokinase plasminogen activator receptor.²⁰ Thus, CK1αLS phosphorylation of hnRNP-C may promote H₂O₂-stimulated vertebrate cell growth. However, in the cytoplasm, cytosolic forms of CK1α (CK1α and CK1αS) play important roles inhibiting key proliferative signaling pathways involving both wnt/β-catenin and the nuclear factor of activated T-cells.^21,22 Thus, it has been unclear whether H₂O₂-activated CK1αLS in the nucleus is promoting H₂O₂-stimulated growth or is, in fact, a compensatory counter-regulatory pathway. Here we demonstrate by selective and stable knockdown of CK1αLS that the kinase is, in fact, an important positive regulator of vascular activation and H₂O₂ mitogenic signaling.     

Apoptosis and proliferation in the neonatal murine heart.

The spatial and temporal patterns of apoptosis and proliferation in timed fetal, neonatal, and adult murine hearts have been determined using an in situ end-labeling technique for detecting fragmented DNA, and bromodeoxyuridine immunofluorescence as a marker for DNA synthesis. Also, cardiac expression of apoptosis-related proteins was assessed by immunofluorescence. Prominent apoptotic labeling was found in the right ventricular subendocardium and the basal septum in the area of the developing conduction system. In the right ventricle, apoptotic labeling surged late in the first day postpartum, then declined to levels similar to the left ventricle by postpartum day 8.5. Apoptotic labeling at the basal septum was greatest peripartum and gradually declined to levels seen in the rest of the heart by postpartum day 8.5. Cessation of proliferation did not occur simultaneously throughout the neonatal heart. Through postpartum day 4.5, incorporation of BrdU was greater in the left ventricle than in the right ventricle, particularly in the subendocardium. Bax and Fas, proapoptotic proteins, were detected homogeneously throughout both ventricles in the neonate, while Bcl-2, an antiapoptotic protein, was not detectable. These data suggest that postnatal cardiac remodeling results from changes in both apoptosis and proliferation. Furthermore, the temporal and spatial pattern of these processes, coincident with the hemodynamic changes associated with parturition, suggests that both processes may be regulated by mechanical factors.