An Investigation of the Inflammatory Landscape in the Brain and Bone Marrow of the APP/PS1 Mouse.

Background: The APP/PS1 mouse model recapitulates pathology of human Alzheimer's disease (AD). While amyloid-ß peptide deposition and neurodegeneration are features of AD, the pathology may involve inflammation and impaired vascular regeneration. Objective: This study evaluated inflammatory environments in the brain and bone marrow (BM), and the impact on brain microvascular density. Methods: BM and frontal cortex from male nine-month-old APP/PS1 or the control C57Bl6/j mice were studied. Vascular density and inflammatory cells were evaluated in the sections of frontal cortex by immunohistochemistry. Different subsets of hematopoietic stem/progenitor cells (BM) and monocyte-macrophages were characterized by flow cytometry and by clonogenic assays. Myelopoietic or inflammatory factors were evaluated by real-time RT-PCR or by western blotting. Results: CD34+ or CD31+ vascular structures were lower (p < 0.01, n = 6) in the frontal cortex that was associated with decreased number of Lin-Sca-1+cKit+ vasculogenic progenitor cells in the BM and circulation (p < 0.02, n = 6) compared to the control. Multipotent progenitor cells MPP4, common lymphoid, common myeloid and myeloid progenitor cells were higher in the APP/PS1-BM compared to the control, which agreed with increased numbers of monocytes and pro-inflammatory macrophages. The expression of pro-myelopoietic factors and alarmins was higher in the APP/PS1 BM-HSPCs or in the BM-supernatants compared to the control. Frontal cortices of APP/PS1 mice showed higher number of pro-inflammatory macrophages (CD11b+F4/80+ or CD80+) and microglia (OX42+Iba1+). Conclusions: These findings show that AD pathology in APP/PS1 mice is associated with upregulated myelopoiesis, which contributes to the brain inflammation and decreased vascularity.

Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymeric Micelles for Improved Gene Delivery of VGF to the Brain through Intranasal Route.

Multifunctional fatty acid grafted polymeric micelles are an effective and promising approach for drug and gene delivery to the brain. An alternative approach to bypass the blood-brain barrier is administration through intranasal route. Multifunctional fatty acid grafted polymeric micelles were prepared and characterized for pVGF delivery to the brain. In vitro pVGF expression was analyzed in bEnd.3 cells, primary astrocytes, and neurons. Comparative in-vivo pVGF expression was analyzed to evaluate the effective route of administration between intranasal and intravenous. Biocompatible, multifunctional polymeric micelles were prepared, having an average size of 200 nm, and cationic zeta potential. Modified polymers were found to be hemo- and cyto-compatible. When transfected with the different modified chitosan formulations, significantly (p < 0.05) higher VGF expression was observed in primary astrocytes and neurons using the mannose, Tat peptide, and oleic acid grafted chitosan polymer. Compared to intravenous administration, intranasal administration of pVGF in polyplex formulation led to significantly (p < 0.05) higher pVGF expression. Developed multifunctional polymeric micelles were an effective pVGF delivery platform to the brain. Mannose and Tat ligand tagging improved the pVGF delivery to the brain.

Improved insulin sensitivity in obese-diabetic mice via chitosan Nanomicelles mediated silencing of pro-inflammatory Adipocytokines.

Obesity induced chronic low-level inflammation is strongly associated with the development of insulin resistance and progression of type-2 diabetes. Systemic treatment with anti-inflammatory therapeutics requires high doses and is associated with serious adverse effects owing to generalized suppression of the immune system. Here we study localized knockdown of pro-inflammatory adipocytokines in adipose tissue macrophages (ATMs) and adipocytes using RNA interference for the treatment of insulin resistance. Chitosan nanomicelles conjugated to ATM and adipocyte targeting ligands were used to transfect short hairpin RNA (shRNA) against tumor necrosis factor-α (TNFα) and monocyte chemoattractant protein-1 (MCP-1). Subcutaneous administration of nanomicellar/pDNA polyplexes in obese-diabetic mice resulted in decreased concentration of pro-inflammatory cytokines TNFα, MCP-1, IL-6, and IL-1ß along with increased concentration of insulin-sensitizing adipokine adiponectin. Downregulation of inflammatory cytokines resulted in improved insulin sensitivity and glucose tolerance for up to six-weeks following single dose, compared to untreated obese-diabetic mice.

Rice pest management with reduced risk pesticides in India.

Sitapur district in the Uttar Pradesh (U.P.) state of northern India has been observed to consume large amounts of WHO classified "extremely" and "highly hazardous" pesticides, in rice crop, posing significant health and environmental threats. Keeping in view this problem, integrated pest management (IPM) modules were synthesized for rice crop and then compared with non-IPM/farmer's practice (NIPM). This study assisted in identifying pesticides with reduced risk to the environment. To measure and compare risks, environmental impact quotient (EIQ) has been used as a pesticide risk indicator model, between IPM and NIPM programs. Using this model, the field EIQ values (EIQ field use rating or EIQ-FUR), for 32 commonly used pesticides in the region, were evaluated based on dosage, frequency, and percent active ingredients present in the pesticide formulations. The results conclude that copper oxychloride (CuOCl2) (50 WP at 1.25 kg/ha) and mancozeb (75 WP at 1.25 kg/ha) were the most detrimental to arthropod parasitoids and were the highest contributors to environmental risk (13-16%), in rice crop. This is based on the comparison of total dosage and active ingredients of pesticides applied under IPM and NIPM, with the total field EIQ values. The IPM modules were observed to have least impact on natural enemies with 30-40% increase in population, while keeping the weed population below 10%. NIPM, on the other hand, had resulted in 20% reduction in crop yields, 50% reduction in biodiversity, and about 150% increase in weed population, relative to the control (untreated) rice fields. Moreover, NIPM practices had been observed to pose 56% greater risk as per the total field EIQ values (62 for IPM and 141 for NIPM). The observations concluded that the EIQ model is a useful tool and can be easily used by the pesticide managers for assessing the risk against NIPM.

Perceptions of Family Among Low-Income Patients With Diabetes in a Text-Based Mobile Health Intervention.

BACKGROUND: Diabetes disproportionately affects the US Latino population, due to socioeconomic pressures, genetics, reduced access to care and cultural practices. While efforts to improve self-care through interventions incorporating family are highly rated by Latinos, family can be both supportive and obstructive. To develop effective interventions, this role needs clarification. METHODS: We conducted group interviews in Spanish and English with 24 participants with diabetes from a mobile health diabetes self-care intervention. We imported transcripts into Dedoose, a qualitative computer analysis program and analyzed them with a modified grounded theory technique. Utilizing an iterative process, we reexamined transcripts with new codes derived in each round of analysis until saturation was reached. We employed techniques to improve trustworthiness (co-coding, member checking). Broad categorical themes arose from the initial codes and were developed into a conceptual model of barriers to and strategies for diabetes management. RESULTS: Family and family responsibilities emerged as both a supportive and obstructive force for diabetes self-care. While the desire to care for family motivated patients, food at family gatherings and pressure from managing multiple family responsibilities contributed to poor diet choices. Yet, some patients believed their diabetes caused their immediate family to make healthier choices. CONCLUSIONS: Among these predominantly Latino patients, family and family responsibilities were key motivators as well as obstacles to self-care, particularly regarding nutrition. Finding the ideal design for social support mHealth-based interventions will require careful study and creation of culturally based programs to match the needs of specific populations, and may require educating family members to provide effective social support.

Blood Product Transfusions and Reactions.

Blood product transfusions are an essential component of the practice of emergency medicine. From acute traumatic hemorrhage to chronic blood loss necessitating transfusion for symptomatic anemia, familiarity with individual blood products and their indications for transfusion is an essential tool for every emergency physician (EP). Although the focus of this article is primarily on the transfusion of red blood cells, many of the concepts are applicable to the transfusion of all blood products. EPs must be fully familiar with both the individual blood components and the potential reactions and complications of these transfusions.

Oncologic Metabolic Emergencies.

Cancer and its therapies may lead to several metabolic emergencies that emergency providers (EPs) should be well-versed in identifying and managing. With prompt recognition and treatment initiation in the emergency department, lives can be saved and quality of life maintained. Most oncologic metabolic emergencies occur in advanced cancer states, but some follow initiation of treatment or may be the presenting syndrome that leads to the cancer diagnosis. This article reviews the 2 most emergent oncologic metabolic diagnoses: tumor lysis syndrome and hypercalcemia of malignancy. A discussion on associated cancers and conditions, pathogenesis and pathophysiology, and management recommendations is included.

Exposure to and Use of Electronic Cigarettes: Does Language Matter?

OBJECTIVES: To determine whether patients who are English proficient become aware of e-cigarettes through different marketing tactics and have dissimilar patterns of use than patients who are non-English speaking. DESIGN: This was a cross-sectional study surveying adult English- and Spanish-speaking patients. ANOVA and chi-squared tests were used to examine differences between groups. SETTING: A large public, safety-net hospital in Los Angeles County, California. RESULTS: Respondents (N=1899) were predominately Hispanic (78%), foreign-born (68%), and reported Spanish as a primary language (64%). Native English speakers reported the highest use of e-cigarettes (26%), followed by non-native (13%) and non-English speakers (2%) (P<.001). In terms of marketing, native and non-native English speakers were more likely to have friends and family as sources of e-cigarette information (P<.001). Native speakers were more likely to see advertisements for e-cigarettes on storefronts (P=.004) and on billboards (P<.001). Non-English speakers were most likely to learn about e-cigarettes on the news (P<.001) and in advertisements on the television and radio (P=.002). Differences in reasons for use were not significant between the three groups. CONCLUSIONS: Native and non-native English speakers become aware of e-cigarettes through different mechanisms and use e-cigarettes at a significantly higher rate than non-English speakers. These results highlight an opportunity for public health programs to concentrate on specific channels of communication that introduce patient populations to e-cigarettes to slow the spread of e-cigarette usage.

High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department.

Earlier intervention in acute HIV infection limits HIV reservoirs and may decrease HIV transmission. We developed criteria for empiric antiretroviral therapy (ART) in an emergency department (ED) routine HIV screening program. We assessed the feasibility and willingness of patients with suspected acute HIV infection in the ED to begin ART. A suspected acute HIV infection was defined as a positive HIV antigen antibody combination immunoassay with pending HIV-antibody differentiation test results and HIV RNA viral load. During the study period, there were 16 confirmed cases of acute HIV infection: 11 met our criteria for empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED against medical advice without a prescription for ART. Eight patients completed at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well received by patients, and offers a unique entry point into the HIV care continuum.

Oncologic metabolic emergencies.

Cancer and its therapies may lead to several metabolic emergencies that emergency providers (EPs) should be well-versed in identifying and managing. With prompt recognition and treatment initiation in the emergency department, lives can be saved and quality of life maintained. Most oncologic metabolic emergencies occur in advanced cancer states, but some follow initiation of treatment or may be the presenting syndrome that leads to the cancer diagnosis. This article reviews the 2 most emergent oncologic metabolic diagnoses: tumor lysis syndrome and hypercalcemia of malignancy. A discussion on associated cancers and conditions, pathogenesis and pathophysiology, and management recommendations is included.

Deep and unusual sialolithiasis of submandibular duct and gland: a surgical dilemma.

Giant solitary submandibular duct calculus and multiple calculi of the gland are extremely rare. This occurrence along with more deep and proximally placed common calculi in submandibular gland may occasionally cause a dilemma in selection of the appropriate surgical approach in the present era of sialoendoscopic surgery. There is a high chance of fracture of the stone in a proximally placed stone in the gland followed by likely dissemination of fragments of the stone into the gland parenchyma during the procedure of sialoendoscopy which is a matter of grave concern. We authors believe that excision of the submandibular gland with the stone in such a situation should still be preferred as the gold standard of treatment leaving the ductal stone for endoscopic removal.

Diagnostic accuracy of venous blood gas electrolytes for identifying diabetic ketoacidosis in the emergency department.

OBJECTIVES: Diagnosing diabetic ketoacidosis (DKA) has traditionally required a venous blood gas (VBG) to obtain serum pH and a serum chemistry panel to obtain electrolyte values. Because newer blood gas analyzers have the ability to report electrolyte values and glucose in addition to pH, this diagnostic process could theoretically be condensed. However, neither the diagnostic accuracy of the VBG for DKA nor the agreement between the VBG electrolytes and the serum chemistry electrolytes, including sodium, chloride, and bicarbonate, has been evaluated in the context of acute hyperglycemia. The purpose of this study was to assess the accuracy of VBG electrolytes for diagnosing DKA using serum chemistry electrolytes measures as the criterion standard and to describe the correlation between VBG and serum chemistry electrolytes in a sample of hyperglycemic patients seen in the emergency department (ED). METHODS: The authors prospectively identified a convenience sample of ED patients with serum blood glucose ≥ 250 mg/dL and examined their paired VBG and serum chemistry electrolytes. The diagnosis of DKA was made by using American Diabetes Association (ADA) criteria including serum glucose ≥ 250 mg/dL, serum anion gap > 10 mEq/L, bicarbonate ≤ 18 mEq/L, serum pH ≤ 7.30, and presence of ketosis. Serum chemistry electrolyte values were considered to be the criterion standard. Diagnostic test characteristics of VBG electrolytes including sensitivity and specificity were compared against this standard. In addition, correlation coefficients for individual electrolytes and anion gap between VBG and chemistry electrolytes were calculated. RESULTS: Paired VBG and serum chemistry panels were available for 342 patients, of whom 46 (13.5%) had DKA. The sensitivity and specificity of the VBG electrolytes for diagnosing DKA was 97.8% (95% confidence interval [CI] = 88.5% to 99.9%) and 100% (95% CI = 98.8% to 100%), respectively. One case of DKA was missed by the VBG. Correlation coefficients between VBG and serum chemistry were 0.90, 0.73, 0.94, and 0.81 for sodium, chloride, bicarbonate, and anion gap, respectively. CONCLUSIONS: The VBG electrolytes were 97.8% sensitive and 100% specific for the diagnosis of DKA in hyperglycemic patients. These preliminary findings support the use of VBG electrolytes in lieu of VBG along with serum chemistry analysis to rule in or rule out DKA.

Prevalence of undiagnosed and suboptimally controlled diabetes by point-of-care HbA1C in unselected emergency department patients.

OBJECTIVES: The objective was to estimate the glycemic control of patients with known diabetes and to assess the prevalence of undiagnosed diabetes in an unselected emergency department (ED) population. Secondary objectives include evaluating the prevalence of undiagnosed diabetes in high-risk groups of ED patients such as Hispanic patients, African Americans, and patients with body mass index (BMI) ≥ 30 kg/m(2) . METHODS: A convenience sample of adult ED patients was screened for diabetes using a National Glycohemoglobin Standardization Program-certified point-of-care (POC) glycated hemoglobin (HbA1C) meter at a single academic medical center during eight 24-hour periods. Diabetes was defined as HbA1C ≥ 6.5%, consistent with new American Diabetes Association (ADA) guidelines. RESULTS: Of the 1,611 patients evaluated in the ED during the study period, 313 were included in the study sample. Of these, 15% reported a history of diabetes, 42% of whom were suboptimally controlled. An additional 14% of the study sample was found to have previously undiagnosed diabetes. In our limited sample, the prevalence of previously undiagnosed diabetes in Hispanics, African Americans, and patients with BMI ≥ 30 kg/m(2) was 14, 27, and 22%, respectively. CONCLUSIONS: Patients in our sample had a high prevalence of suboptimally controlled and undiagnosed diabetes. New POC HbA1C devices and simplified diagnostic criteria for diabetes significantly enhance the possibility of ED-based screening programs. Future research should validate our findings in a broader array of EDs and study the acceptance of such ED-based diabetes screening programs.

Pilomatricoma: Forget me not.

Pilomatricoma is a benign skin neoplasia, which is not commonly encountered in general practice. The diagnosis is often made only after histopathology. The present case report is of a 30-year-old woman who presented with swelling in neck, which was diagnosed as pilomatricoma only after excision. The idea of reporting this case is that pilomatricoma is not rare in occurrence but rarely diagnosed because of lack of confirmation of excised swelling and it is imperative that it should be kept in the differential diagnoses of all superficial skin tumors by dermatologists and surgeons.

Fungal granuloma in external auditory canal.

Aural masses are most commonly inflammatory in nature, but may also manifest as more severe disease making them an important differential diagnoses. We present the case of a 20-year-old female who presented with a 3-month history of unilateral, foul smelling, occasionally blood stained ear discharge and earache. She was conservatively treated for these 3 months and was subsequently referred to our institute where she was diagnosed with a mass left ear. After thorough evaluation an excision biopsy with histopathological examination was done which proved the mass to be a fungal granuloma. The importance of this case report lies in the statement that in a case presenting with chronic foul smelling ear discharge fungal granuloma should be kept in the differential diagnoses.