The development of a research human milk bank.

Although there are well-established clinical human milk banks in the United States, there are no milk banks specifically intended to foster research on human milk. The authors' goal was to establish a milk bank with a core data set to support exploratory and hypothesis-driven studies on human milk. Donations to the Cincinnati Children's Research Human Milk Bank are accepted within the context of ongoing, hypothesis-driven research or on an ad hoc basis. Donors must give informed consent, and scientists wishing to use the samples must have Institutional review board approval for their use. Development of more research human milk banks can potentially provide resources for multidisciplinary collaboration and advance the study of human milk and lactation.     

Association between increased levels of TNF-alpha, decreased levels of prealbumin and retinol-binding protein, and disease outcome

We determined whether there is an association between tumor necrosis factor-alpha (TNF-alpha), undernutrition [prealbumin (PA) <160 mg/L, retinol binding protein (RBP) <30 mg/L], disease stage, outcome (death or survival), and race in children with leukemia. TNF-alpha, PA, and RBP were measured in 52 patients (0.8 to 17 years old): 18 African Americans, 34 whites; 27 newly diagnosed (ND), and 25 in clinical remission (CR). Mean levels of TNF-alpha were higher in patients than in 46 healthy children (p < 0.05), but were not different between ND and CR groups. Mean acute phase proteins (APP) were different among groups: ND > CR > controls (p < 0.05). Mean levels of PA and RBP were lower in patients than in controls (p < 0.051, and tended to be higher in CR than in ND patients. African-American patients had lower concentrations of TNF-alpha, PA, and RBP but higher APP than white patients (p < 0.05). CR patients and African-American patients who died tended to have higher levels of TNF-alpha and APP, but lower PA and RBP than those who survived. A higher percentage of ND African Americans (45%) than of ND whites (13%) died. Results suggest that undernutrition and inflammation in CR patients and African Americans were associated with poor survival, and that ND African Americans have a poorer outcome than whites independently of TNF-alpha levels.     

Differential regulation of IL-13 and IL-4 production by human CD8+ and CD4+ Th0, Th1 and Th2 T cell clones and EBV-transformed B cells

In the present study, the requirements and characteristics forthe production of IL-13 by human T cells, T cell clones andB cells were determined and compared with those of IL-4. IL-13was produced by human CD4⁺ and CD8⁺ T lymphocyte subsets isolatedfrom peripheral blood mononuclear cells and by CD4⁺ and CD8⁺T cell clones. CD4⁺ T cell clones belonging to T_h0, T_h1-likeand T_h2-like subsets produced IL-13 following antigen-specificor polyclonal activation. In addition, EBV-transformed B celllines expressed IL-13 mRNA and produced small amounts of IL-13protein. Expression of IL-13 mRNA and production of IL-13 proteinby peripheral blood T cells and T cell clones was induced rapidlyand was relatively long lasting, whereas IL-4 production bythese cells was transient In addition, IL-13 mRNA expressionwas induced by modes of activation that failed to induce IL-4mRNA expression. IL-13 shares many biological activities withIL-4 which Is compatible with the notion that the IL-13 andIL-4 receptors share a common component required for signaltransduction. However, IL-13 lacks the T cell-activating propertiesof IL-4. Here we have shown that this is related to the factthat T cells fall to bind radiolabeled IL-13 and do not expressthe IL-13-speclflc receptor component Taken together, theseresults indicate that the differences In expression and biologicalactivities of IL-4 and IL-13 on T cells may have consequencesfor the relative roles of these cytokines In the immune response.     

Autistic Traits,Empathizing–Systemizing,and Gender Diversity

Archives of Sexual Behavior - Previous research indicates a link between autism and transgender and gender-diverse identities, though the association is not yet fully understood. The current study...     

An Intelligent System to Enhance the Performance of Brain Tumor Diagnosis from MR Images

Journal of Digital Imaging - In the human body, cancer is caused by aberrant cell proliferation. Brain tumors are created when cells in the human brain proliferate out of control. Brain tumors...     

In the footsteps of "Arundhati": Asian Indian women's experience of domestic violence in the United States

This study examined the ideologies and conditions that are creating women's vulnerability to spousal abuse in the Asian Indian community in the US. The study focused on the multiple factors involved in Asian Indian women's experiences of domestic violence in the US: their minority status, life as an immigrant, and pressures to preserve a flawless public image of their community. The data were collected from interviews with 12 highly educated women from India who had sought outside help due to spousal abuse. 10 of these women were foreign born, and 2 were brought up in the US. The study revealed that the most important factor in these women's lives seemed to be childhood indoctrination into the ideals of ?good? wife and mother that include sacrifice of personal freedom and autonomy. Although majority of the women worked as professionals, economic independence did not seem to provide them with a sense of empowerment. Furthermore, they felt responsible for the reputation of their families in India, were eager not to compromise their families' honor with a divorce, and operated under the added pressures of preserving traditions and presenting an ?unblemished? image of the community to the US mainstream.     

Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer: A Retrospective Matched Case-Control Study

Background

Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.

INAUGURAL ARTICLE by a Recently Elected Academy Member:Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials

Existing drugs are slow to eradicate Mycobacterium tuberculosis (Mtb) in patients and have failed to control tuberculosis globally. One reason may be that host conditions impair Mtb’s replication, reducing its sensitivity to most antiinfectives. We devised a high-throughput screen for compounds that kill Mtb when its replication has been halted by reactive nitrogen intermediates (RNIs), acid, hypoxia, and a fatty acid carbon source. At concentrations routinely achieved in human blood, oxyphenbutazone (OPB), an inexpensive anti-inflammatory drug, was selectively mycobactericidal to nonreplicating (NR) Mtb. Its cidal activity depended on mild acid and was augmented by RNIs and fatty acid. Acid and RNIs fostered OPB’s 4-hydroxylation. The resultant 4-butyl-4-hydroxy-1-(4-hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione (4-OH-OPB) killed both replicating and NR Mtb, including Mtb resistant to standard drugs. 4-OH-OPB depleted flavins and formed covalent adducts with N-acetyl-cysteine and mycothiol. 4-OH-OPB killed Mtb synergistically with oxidants and several antituberculosis drugs. Thus, conditions that block Mtb’s replication modify OPB and enhance its cidal action. Modified OPB kills both replicating and NR Mtb and sensitizes both to host-derived and medicinal antimycobacterial agents.Some bacterial infections can be cured with a single dose of an antibiotic, and most others can be cured with administration of one drug over several days or weeks. In contrast, routine treatment of drug-sensitive tuberculosis (TB) takes 2 mo of therapy with four drugs and an additional 4 mo with two drugs to reduce the 2-y relapse rate below 5%. The difficulty of completing prolonged treatment is a major reason for emergence of drug resistance. When the infecting strain is resistant to isoniazid and rifampin, the two drugs recommended for all 6 mo of treatment, cure often requires 2 y of daily administration of toxic, expensive, second-line agents that are often unavailable at the point of care. When the causative strain is additionally resistant to a quinolone and an aminoglycoside, the resultant “extensively drug-resistant” TB was fatal to 80% of patients in a leading center (1), although complex multidrug regimens have achieved higher cure rates in populations not previously exposed to the additional drugs (2). In addition to sharing air with someone with TB, leading risk factors for contracting the disease are malnutrition, HIV infection, diabetes, and exposure to smoke from cigarettes or cooking fires (3). These epidemiological challenges exacerbate problems of inadequate diagnostic technology and limited access to drug susceptibility testing and to drugs. Control of the pandemic is not in sight (3).It is widely hypothesized that treatment of TB is protracted because nonreplicating (NR) subpopulations of bacilli are phenotypically tolerant to drugs that were selected for activity against replicating (R) Mycobacterium tuberculosis (Mtb) (4). Mtb can occupy diverse microenvironments in the host. Evidence from auxotrophs, analyses of gene expression, and direct and indirect biochemical measurements in vivo or ex vivo in experimental animals and people suggest that such environments expose Mtb to acid, hypoxia, reactive nitrogen intermediates (RNIs), oxidative stress, carbohydrate deficiency, and metal starvation or intoxication, and require Mtb to metabolize fatty acids or cholesterol (5–17). In vitro, many of the same conditions can make Mtb relatively refractory to killing by the standard agents, except for pyrazinamide, which is only effective at a low pH.Thus, there is a need for a high-throughput screen (HTS) for compounds that kill Mtb when the Mtb has been rendered NR by a combination of physiologically relevant host-imposed conditions. We were encouraged to devise such a screen by recent discoveries of a class of compounds that kill Mtb only when it is NR (18), an antibiotic in clinical use for other infections that kills NR Mtb better than R Mtb (19), and a compound that kills NR and R Mtb equally well (20). Unfortunately, only one of those compounds is an approved drug, and even if it were of proven utility in TB, its price would preclude its use by most of those who need it. We decided to screen other existing drugs that are not regarded as antiinfectives for those that kill NR Mtb. Here, we report finding such a drug in an HTS that combined four host-imposed conditions, some of which converted the drug into a form active on both R and NR Mtb.