An Update on the Status of Potent Inhibitors of Metallo-β-Lactamases

The production of metallo-β-lactamases is the most important strategy by which pathogenic bacteria become resistant to currently known β-lactam antibiotics. The emergence of these enzymes is particularly concerning for the future treatment of bacterial infections. There are no clinically available drugs capable of inhibiting any of the metallo-β-lactamases, so there is an urgent need to find such inhibitors. In this review, an up-to-date status of the inhibitors investigated for the inhibition of metallo-β-lactamases has been given so that this rich source of structural information of presently known metallo-β-lactamases could be helpful in generating a broad-spectrum potent inhibitor of metallo-β-lactamases.     

A study with Bangladeshi women: Seeking care for breast health

In many low- and middle-income countries, breast cancer survival is low. Reasons for this are multifactorial, but delayed presentation for care is a common theme. In this survey study with 100 urban Bangladeshi women, we examined the role of socioeconomic and sociocultural factors on their likelihood to seek breast care from a family physician. In our multivariate model, a woman's age and education significantly predicted her likelihood to see a physician. Sociocultural aspects (e.g., concerns about time commitment of family members, personal household obligations) were significant at bivariate level. Findings are discussed in relation to practice, policy, and research.     

Pork Consumption and Seroprevalence of Hepatitis E Virus,Thailand, 2007–2008

The nationwide seroprevalence of hepatitis E IgG was determined among young men in Thailand. Overall seroprevalence was 14% (95% CI 13%–15%); range by province was 3%–26%. Seroprevalence was lowest in the south, an area predominantly occupied by persons of the Islam religion, whose dietary laws proscribe pork.     

Natural and anthropogenic radioactivity levels and the associated radiation hazard in the soil of Oodalia Tea Estate in the hilly region of Fatickchari in Chittagong,Bangladesh

Radioactivity in the soil of a tea garden in the Fatickchari area in Chittagong, Bangladesh, was measured using a high-resolution HPGe detector. The soil samples were collected from depths of up to 20 cm beneath the soil surface. The activity concentrations of naturally occurring ²³⁸U and ²³²Th were observed to be in the range of 27 ± 7 to 53 ± 8 Bq kg⁻¹ and 36 ± 11 to 72 ± 11 Bq kg⁻¹, respectively. The activity concentration of ⁴⁰K ranged from 201 ± 78 to 672 ± 81 Bq kg⁻¹, and the highest activity of fallout ¹³⁷Cs observed was 10 ± 1 Bq kg⁻¹. The average activity concentration observed for ²³⁸U was 39 ± 8 Bq kg⁻¹, for ²³²Th was 57 ± 11 Bq kg⁻¹, for ⁴⁰K was 384 ± 79 Bq kg⁻¹ and for ¹³⁷Cs was 5 ± 0.5 Bq kg⁻¹. The radiological hazard parameters (representative level index, radium equivalent activity, outdoor and indoor dose rates, outdoor and indoor annual effective dose equivalents, and radiation hazard index) were calculated from the radioactivity in the soil.     

Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis

This study was designed to examine stool specimens of irritable bowel syndrome (IBS) patients for Blastocystis hominis, a common intestinal parasite. One hundred fifty patients were enrolled, 95 IBS cases and 55 controls. These patients provided a medical history, and underwent physical and laboratory evaluations that included stool microscopy and culture for B. hominis and colonoscopy. The 95 cases (51 males and 44 females) had a mean +/- SD age of 37.8 +/- 13.2 years. Stool microscopy was positive for B. hominis in 32% (30 of 95) of the cases and 7% (4 of 55) of the controls (P = 0.001). Stool culture was positive in 46% (44 of 95) of the cases and 7% (4 of 55) of the controls (P < 0.001). Stool culture for B. hominis in IBS was more sensitive than microscopy (P < 0.001). Blastocystis hominis was frequently demonstrated in the stool samples of IBS patients; however, its significance in IBS still needs to be investigated. Stool culture has a higher positive yield for B. hominis than stool microscopy.     

Haematological Reconstitution after Autografting for Chronic Granulocytic Leukaemia in Transformation: the Influence of Previous Splenectomy

S ummary Peripheral blood values and bone marrow appearances were monitored in eight patients treated for chronic granulocytic leukaemia in transformation by cytotoxic drugs with or without total body irradiation followed by autografting with cryopreserved-thawed peripheral blood nucleated cells. One of the patients was 'autografted' on two occasions. Five patients had been splenectomized early in the first chronic phase and the other three patients had their spleens intact. Recovery of peripheral blood values was more rapid in the splenectomized than in the non-splenectomized patients. CFUc were present in the circulation immediately after autografting in each case but subsequently the pattern of CFUc changes differed between patients. The bone marrow was hypocellular at the time of autografting but the rate at which it returned to a typical chronic phase picture varied. Peripheral blood nucleated cells collected at the time of diagnosis include stem cells with the capacity to repopulate the marrow after 'ablative' therapy for transformation. Elective splenectomy in the chronic phase may promote more rapid recovery of peripheral blood values but its long-term importance is unknown.     

Increased mitochondrial function downstream from KDM5A histone demethylase rescues differentiation in pRB-deficient cells

The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cell cycle progression. Increasing evidence suggests that pRb also promotes differentiation, but the mechanisms are poorly understood, and the key question remains as to how differentiation in tumor cells can be enhanced in order to diminish their aggressive potential. Previously, we identified the histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein counteracting pRB''s role in promoting differentiation. Here we show that loss of Kdm5a restores differentiation through increasing mitochondrial respiration. This metabolic effect is both necessary and sufficient to induce the expression of a network of cell type-specific signaling and structural genes. Importantly, the regulatory functions of pRB in the cell cycle and differentiation are distinct because although restoring differentiation requires intact mitochondrial function, it does not necessitate cell cycle exit. Cells lacking Rb1 exhibit defective mitochondria and decreased oxygen consumption. Kdm5a is a direct repressor of metabolic regulatory genes, thus explaining the compensatory role of Kdm5a deletion in restoring mitochondrial function and differentiation. Significantly, activation of mitochondrial function by the mitochondrial biogenesis regulator Pgc-1α (peroxisome proliferator-activated receptor γ-coactivator 1α; also called PPARGC1A) a coactivator of the Kdm5a target genes, is sufficient to override the differentiation block. Overexpression of Pgc-1α, like KDM5A deletion, inhibits cell growth in RB-negative human cancer cell lines. The rescue of differentiation by loss of KDM5A or by activation of mitochondrial biogenesis reveals the switch to oxidative phosphorylation as an essential step in restoring differentiation and a less aggressive cancer phenotype.