Effect of lactose standardization of milk using low-concentration factor ultrafiltration: Effect of reducing the lactose-to-casein ratio on the properties of milled-curd Cheddar cheese.

The pH of cheese is determined by the amount of lactose fermented and the buffering capacity of the cheese. The buffering capacity of cheese is largely determined by the protein contents of milk and cheese and the amount of insoluble calcium phosphate in the curd, which is related to the rate of acidification. The objective of this study was to standardize both the lactose and casein contents of milk to better control final pH and prevent the development of excessive acidity in Cheddar cheese. This approach involved the use of low-concentration factor ultrafiltration of milk to increase the casein content (∼5%), followed by the addition of water, ultrafiltration permeate, or both to the retentate to adjust the lactose content. We evaluated milks with 4 different lactose-to-casein ratios (L:CN): 1.8 (control milk), 1.4, 1.1, and 0.9. All cheesemilks had similar total casein (2.3%) and fat (3.4%) contents. These milks were used to make milled-curd Cheddar cheese, and we evaluated cheese composition, texture, functionality, and sensory properties over 9 mo of ripening. Cheeses made from milks with varying levels of L:CN had similar moisture, protein, fat, and salt contents, due to slight modifications during manufacture (i.e., cutting the gel at a smaller size than control) as well as control of acid development at critical steps (i.e., cutting the gel, whey drainage, salting). As expected, decreasing the L:CN led to cheeses with lower lactic acid, residual lactose, and insoluble Ca contents, as well as a substantial pH increase during cheese ripening in cheeses. The L:CN ratio had no significant effect on the levels of primary and secondary proteolysis. Texture profile analysis showed no significant differences in hardness values during ripening. Maximum loss tangent, an index of cheese meltability, was lower until 45 d for the L:CN 1.4 and 0.9 treatments, but after 45 d, all reduced L:CN cheeses had higher maximum loss tangent values than the control cheese (L:CN 1.8). Sensory analyses showed that cheeses made from milks with reduced L:CN contents had lower acidity, sourness, sulfury notes, and chewdown cohesiveness. Standardization of milk to a specific L:CN ratio, while maintaining a constant casein level in the milk, would allow Cheddar cheese manufacturers to have tighter control of pH and acidity.

Spectral Decomposition of the Flow and Characterization of the Sound Signals through Stenoses with Different Levels of Severity.

Treatments of atherosclerosis depend on the severity of the disease at the diagnosis time. Non-invasive diagnosis techniques, capable of detecting stenosis at early stages, are essential to reduce associated costs and mortality rates. We used computational fluid dynamics and acoustics analysis to extensively investigate the sound sources arising from high-turbulent fluctuating flow through stenosis. The frequency spectral analysis and proper orthogonal decomposition unveiled the frequency contents of the fluctuations for different severities and decomposed the flow into several frequency bandwidths. Results showed that high-intensity turbulent pressure fluctuations appeared inside the stenosis for severities above 70%, concentrated at plaque surface, and immediately in the post-stenotic region. Analysis of these fluctuations with the progression of the stenosis indicated that (a) there was a distinct break frequency for each severity level, ranging from 40 to 230 Hz, (b) acoustic spatial-frequency maps demonstrated the variation of the frequency content with respect to the distance from the stenosis, and (c) high-energy, high-frequency fluctuations existed inside the stenosis only for severe cases. This information can be essential for predicting the severity level of progressive stenosis, comprehending the nature of the sound sources, and determining the location of the stenosis with respect to the point of measurements.

Spectral Decomposition and Sound Source Localization of Highly Disturbed Flow through a Severe Arterial Stenosis.

For the early detection of atherosclerosis, it is imperative to explore the capabilities of new, effective noninvasive diagnosis techniques to significantly reduce the associated treatment costs and mortality rates. In this study, a multifaceted comprehensive approach involving advanced computational fluid dynamics combined with signal processing techniques was exploited to investigate the highly turbulent fluctuating flow through arterial stenosis. The focus was on localizing high-energy mechano-acoustic source potential to transmit to the epidermal surface. The flow analysis results showed the existence of turbulent pressure fluctuations inside the stenosis and in the post-stenotic region. After analyzing the turbulent kinetic energy and pressure fluctuations on the flow centerline and the vessel wall, the point of maximum excitation in the flow was observed around two diameters downstream of the stenosis within the fluctuating zone. It was also found that the concentration of pressure fluctuation closer to the wall was higher inside the stenosis compared to the post-stenotic region. Additionally, the visualization of the most energetic proper orthogonal decomposition (POD) mode and spectral decomposition of the flow indicated that the break frequencies ranged from 80 to 220 Hz and were correlated to the eddies generated within these regions.

Health implications of sex trading characteristics in Long Beach, California, USA.

This study examined the comparative health risk behaviors of women who (a) traded sex for money, (b) traded sex for drugs, (c) traded sex for both drugs and money, or (d) did not trade sex. Self-report data were collected from 2369 women who received services through HIV and sexually transmitted infection (STI) testing programs and a subset were tested for HIV, hepatitis B, hepatitis C, and syphilis. Results revealed those women who traded sex only for money used condoms, were tested for HIV, and received the HIV test results more often than the other women. Women who traded sex for both drugs and money reported a significantly higher prevalence of gonorrhea, hepatitis B, and syphilis; were more likely to test positive for hepatitis B, syphilis, and HIV; engaged more often in sex acts without condoms; and were incarcerated for significantly more days. Based on these findings, the targets with greatest potential for STI prevention interventions are female sex workers who trade sex for both drugs and money.

Dendritic peptide bolaamphiphiles for siRNA delivery to primary adipocytes.

Obesity is a major risk factor for diabetes, heart disease and other health problems. Adipose tissue plays a central role in the development of obesity and obesity-associated diseases. Gene therapy targeting adipose tissue may provide a promising strategy for obesity treatment. However, nucleic acid delivery to adipose tissue or even cultured adipocytes is challenging due to low delivery efficacy and high toxicity of the current cationic lipid based delivery systems, or monoamphiphiles. Herein, we report using dendritic peptide bolaamphiphiles (bolas) to deliver siRNA to primary adipocytes and hepatocytes. The bola consists of two l-Lysine dendrons connected to a fluorocarbon core through disulfide linkages. The Lysine dendrons are functionalized with l-histidine and l-tryptophan to promote endosomal escape and cellular uptake. The bola exhibited over 70% knockdown of GAPDH gene in both primary adipocytes and hepatocytes. Importantly, different from Lipofectamine that significantly reduced genes involved in lipolysis, lipogenesis, fatty acid oxidation and ketogenesis, the bolas had little to no effect on these genes. These results demonstrate the bola as a promising new vector for clinical and experimental applications for delivery of siRNA to metabolic organs.

Measuring the Frequency Occurrence of Handwriting and Handprinting Characteristics.

The premise of this study was to take a valid population sampling of handwriting and handprinting and assess how many times each of the predetermined characteristic is found in the samples. Approximately 1500 handwriting specimens were collected from across the United States and pared to obtain a representative sample of the U.S. adult population according to selected demographics based on age, sex, ethnicity, handedness, education level, and location of lower-grade school education. This study has been able to support a quantitative assessment of extrinsic and intrinsic effects in handwriting and handprinting for the six subgroups. Additional results include analyses of the interdependence of characteristics. This study found that 98.55% of handprinted characteristics and 97.39% of cursive characteristics had an independence correlation of under 0.2. The conclusions support use of the product rule in general, but with noted caveats. Finally, this study provides frequency occurrence proportions for 776 handwriting and handprinting characteristics.

A Head-to-Head Comparative Phase II Study of Standard Urine Culture and Sensitivity Versus DNA Next-generation Sequencing Testing for Urinary Tract Infections.

Many studies have discussed clinical practice guidelines for the treatment of cystitis and pyelonephritis. Treatment of uncomplicated urinary tract infections (UTIs) can be based on empiric antibiotic therapy. For complicated or recurrent UTIs, therapy can be based on laboratory-controlled culture and sensitivity (C&S) reports. The diagnosis of UTI by clinical criteria alone has an error rate of up to 33%. In addition, positive laboratory culture results do not always indicate a diagnosis of UTI. Comparison of urine in a conventional culture model versus DNA next-generation sequencing (NGS) to accurately identify and provide information on resistance factors (mobile genetic elements) is warranted. Our study was a head-to-head comparative phase II study of standard urine C&S versus DNA NGS testing for the diagnosis and treatment efficacy in patients with symptoms of acute cystitis based on short-term outcomes.

Focused Library Approach to Discover Discrete Dipeptide Bolaamphiphiles for siRNA Delivery.

In this study, we report a new dipeptide functionalization strategy for developing new dendritic bolaamphiphile vectors for efficient siRNA transfection. A focused library of dipeptides was constructed using four amino acids: l-arginine, l-histidine, l-lysine, and l-tryptophan. The dipeptides were coupled to two dendritic bolaamphiphile scaffolds that we developed previously, allowing us to quickly access a focused library of discrete vectors with multivalent dendritic dipeptide functionalities. The resulting discrete bolaamphiphiles were screened for siRNA delivery in vitro in HEK-293 and HeLa cells. Bolaamphiphiles functionalized with dipeptides containing Lys or Arg and either His or Trp were the most effective for in vitro siRNA delivery. Necessary cationic charge to ensure efficient siRNA binding are provided by Arg and Lys residues, whereas endosomal escape is provided through pH responsive buffering of His or membrane interactions of Trp. The most effective vectors (F10 HR/RH) exhibited greater than 75% gene silencing in multiple cell lines and exhibited serum stability.

Fluorocarbon Modified Low-Molecular-Weight Polyethylenimine for siRNA Delivery.

We report the synthesis and study of fluorocarbon (FC) modified polyethylenimine (PEI) for the purpose of siRNA delivery. Low-molecular-weight PEI (Mn = 600) was functionalized with fluorocarbon epoxides of varying length. All FC-modified samples with greater than 2.0 equiv of FC epoxide per PEI induced potent gene silencing in vitro. Compared to hydrocarbon (HC) analogues, the FC vectors showed greater general silencing efficacy, higher cell uptake, and reduced association with serum components. Collectively, the data suggest that modification of polyamines with FCs is a promising approach for the discovery of novel vectors for siRNA delivery.

Mental Health Research in Correctional Settings: Perceptions of Risk and Vulnerabilities.

With over half of individuals incarcerated having serious mental health concerns, correctional settings offer excellent opportunities for epidemiological, prevention, and intervention research. However, due to unique ethical and structural challenges, these settings create risks and vulnerabilities for participants not typically encountered in research populations. We surveyed 1,224 researchers, IRB members, and IRB prisoner representatives to assess their perceptions of risks associated with mental health research conducted in correctional settings. Highest-ranked risks were related to privacy, stigma, and confidentiality; lowest-ranked risks were related to prisoners' loss of privileges or becoming targets of violence due to having participated in research. Cognitive impairment, mental illness, lack of autonomy, and limited access to services emerged as the greatest sources of vulnerability; being male, being female, being over age of 60, being a minority, and being pregnant were the lowest-ranked sources of vulnerability. Researchers with corrections experience perceived lower risks and vulnerabilities than all other groups, raising the question whether these researchers accurately appraise risk and vulnerability based on experience, or if their lower risk and vulnerability perceptions reflect potential bias due to their vested interests. By identifying areas of particular risk and vulnerability, this study provides important information for researchers and research reviewers alike.

Knowledge of Federal Regulations for Mental Health Research Involving Prisoners.

BACKGROUND: Given their vulnerability to coercion and exploitation, prisoners who participate in research are protected by Office for Human Research Protections (OHRP) regulations designed to ensure their safety and wellbeing. Knowledge of these regulations is essential for researchers who conduct and institutional review boards (IRBs) that oversee mental health research in correctional settings. METHODS: We explored depth of knowledge of OHRP regulations by surveying a nationwide sample of: (1) mental health researchers who have conducted research in correctional settings; (2) mental health researchers who have conducted research in non-correctional settings; (3) IRB members who have overseen mental health research in correctional settings; (4) IRB members who have overseen mental health research in in non-correctional settings; and (5) IRB prisoner representatives. Participants responded to a 10-item knowledge questionnaire based on OHRP regulations. RESULTS: 1,256 participants provided usable data (44.9% response rate). Results revealed limited knowledge of OHRP regulations, with a mean across groups of 44.1% correct answers. IRB Prisoner representatives, IRB members, and researchers with correctional experience demonstrated the highest levels of knowledge; however, even these participants were able to correctly answer only approximately 50% of the items. CONCLUSIONS: Although awareness that prisoners are a protected population and that different regulatory procedures apply to research with them is likely to be universal among researchers and IRB members, our findings reveal limited mastery of the specific OHRP regulations that are essential knowledge for researchers who conduct and IRB members who oversee mental health research in correctional settings. Given well-documented health and healthcare disparities, prisoners could potentially benefit greatly from mental health research; increasing knowledge of the OHRP regulations among researchers and IRB members is a crucial step toward meeting this important public health goal.

Structure-Based Design of Dendritic Peptide Bolaamphiphiles for siRNA Delivery.

Development of safe and effective delivery vectors is a critical challenge for the application of RNA interference (RNAi)-based biotechnologies. In this study we show the rational design of a series of novel dendritic peptide bolaamphiphile vectors that demonstrate high efficiency for the delivery of small interfering RNA (siRNA) while exhibiting low cytotoxicity and hemolytic activity. Systematic investigation into structure-property relationships revealed an important correlation between molecular design, self-assembled nanostructure, and biological activity. The unique bolaamphiphile architecture proved a key factor for improved complex stability and transfection efficiency. The optimal vector contains a fluorocarbon core and exhibited enhanced delivery efficiency to a variety of cell lines and improved serum resistance when compared to hydrocarbon analogues and lipofectamine RNAiMAX. In addition to introducing a promising new vector system for siRNA delivery, the structure-property relationships and "fluorocarbon effect" revealed herein offer critical insight for further development of novel materials for nucleic acid delivery and other biomaterial applications.

Key Stakeholders' Perceptions of Motivators for Research Participation Among Individuals Who Are Incarcerated.

Understanding motivations of research participants is crucial for developing ethical research protocols, especially for research with vulnerable populations. Through interviews with 92 institutional review board members, prison administrators, research ethicists, and researchers, we explored key stakeholders' perceptions of what motivates incarcerated individuals to participate in research. Primary motivators identified were a desire to contribute to society, gaining knowledge and health care, acquiring incentives, and obtaining social support. The potential for undue influence or coercion were also identified as motivators. These results highlight the need for careful analysis of what motivates incarcerated individuals to participate in research as part of developing or reviewing ethically permissible and responsible research protocols. Future research should expand this line of inquiry to directly include perspectives of incarcerated individuals.

HIV/AIDS Research in Correctional Settings: A Difficult Task Made Even Harder?

Housing a large number of individuals living with or at risk for HIV/AIDS, correctional settings have considerable potential for epidemiological, prevention, and treatment research. However, federal regulations and institutional challenges have limited the extent and types of such research with prisoners. This study examines the degree to which HIV/AIDS correctional researchers report greater challenges than do their noncorrectional counterparts. Results indicate that correctional researchers reported significantly more frequent challenges than those in noncorrectional settings, even after controlling for experience, with the dominant difference related to challenges due to the research setting. These findings add empirical data and support previous research in the field; however, additional research should include correctional staff and incarcerated individuals, and explore whether these differences extend to other research topics.

HIV/AIDS research in correctional settings: perspectives on training needs from researchers and IRB members.

Being disproportionately represented by individuals living with HIV/AIDS, correctional facilities are an important venue for potentially invaluable HIV/AIDS epidemiological and intervention research. However, unique ethical, regulatory, and environmental challenges exist in these settings that have limited the amount and scope of research. We surveyed 760 HIV/AIDS researchers, and IRB chairs, members, and prisoner representatives to identify areas in which additional training might ameliorate these challenges. Most commonly identified training needs related to federal regulations, ethics (confidentiality, protection for participants/researchers, coercion, privacy, informed consent, and general ethics), and issues specific to the environment (culture of the correctional setting; general knowledge of correctional systems; and correctional environments, policies, and procedures). Bolstering availability of training on the challenges of conducting HIV/AIDS research in correctional settings is a crucial step toward increasing research that will yield significant benefits to incarcerated individuals and society as a whole.

Evaluation of NaCl, pH, and lactic acid on the growth of Shiga toxin-producing Escherichia coli in a liquid Cheddar cheese extract.

A Cheddar cheese model system, Cheddar cheese extract, was used to examine how different levels of known microbial hurdles (NaCl, pH, and lactic acid) in Cheddar cheese contribute to inhibition of bacterial pathogens. This knowledge is critical to evaluate the safety of Cheddar varieties with altered compositions. The range of levels used covered the lowest and highest level of these factors present in low-sodium, low-fat, and traditional Cheddar cheeses. Four pathogens were examined in this model system at 11 °C for 6 wk, with the lowest levels of these inhibitory factors that would be encountered in these products. The 4 pathogens examined were Salmonella enterica, Staphylococcus aureus, Listeria monocytogenes, and Shiga toxin-producing Escherichia coli (STEC). None of these organisms were capable of growth under these conditions. The STEC exhibited the highest survival and hence was used to examine which of these inhibitory factors (NaCl, pH, and lactic acid) was primarily responsible for the observed inhibition. The STEC survival was examined in Cheddar cheese extract varying in NaCl (1.2 vs. 4.8%), lactic acid (2.7 vs. 4.3%), and pH (4.8 vs. 5.3) at 11 °C for 6 wk. The microbial hurdle found to have the greatest effect on STEC survival was pH. The interactions between pH and levels of protonated lactic acid and anionic lactic acid with STEC survival was also evaluated; only the concentration of protonated lactic acid was determined to have a significant effect on STEC survival. These results indicate that, of the pathogens examined, STEC is of the greatest concern in Cheddar varieties with altered compositions and that pH is the microbial hurdle primarily responsible for controlling STEC in these products.

College students' knowledge about fetal alcohol spectrum disorder.

BACKGROUND: Fetal Alcohol Spectrum Disorders (FASDs) are the leading known preventable birth defects in North America. Knowledge surveys about FASD have been conducted with various health and allied healthcare providers and have proven useful in identifying gaps in knowledge and differences among provider groups to support prevention efforts. To date, no research has been conducted exploring FASD knowledge among college students. OBJECTIVE: This study explored FASD knowledge in a sample of college students, a group at particularly high risk for alcohol-exposed pregnancies. Findings are compared to professionals in several healthcare and affiliated professional groups who were previously surveyed with the same FASD-related items. METHODS: Surveys from 1,035 college students at a northwestern university were analyzed. Included with the ACHA-National College Health Assessment II were questions regarding FASD. College students' knowledge was compared with that of professionals in key healthcare and affiliated positions to define their relative awareness of FASD risk. RESULTS: Overall, findings revealed adequate FASD knowledge among college students. Although minor differences emerged when comparing students and professionals' responses, most respondent groups answered with an 85% accuracy rate or higher. CONCLUSION: College students demonstrated adequate knowledgeable about FASD. Future research must explore whether such knowledge translates into lower risk behavior and consequent reduction in alcohol-exposed pregnancies.

Conducting Ethical Research with Correctional Populations: Do Researchers and IRB Members Know the Federal Regulations?

Conducting or overseeing research in correctional settings requires knowledge of specific federal rules and regulations designed to protect the rights of individuals in incarceration. To investigate the extent to which relevant groups possess this knowledge, using a 10-item questionnaire, we surveyed 885 IRB prisoner representatives, IRB members and chairs with and without experience reviewing HIV/AIDS correctional protocols, and researchers with and without correctional HIV/AIDS research experience. Across all groups, respondents answered 4.5 of the items correctly. Individuals who have overseen or conducted correctional research had the highest scores; however, even these groups responded correctly only to slightly more than half of the items. These findings emphasize the need for ongoing training in federal guidelines governing correctional research, particularly for those individuals who are embarking on this type of research.

Alternative and complementary treatment needs and experiences of women with breast cancer.

OBJECTIVES: The study objectives were to explore the potential need for and use of complementary and alternative (CAM) services among women diagnosed with breast cancer and to investigate reasons for nonreceipt of CAM. DESIGN: The Alaska Breast Cancer Needs Assessment Survey was completed by female breast cancer survivors in Alaska. The survey assessed physical and psychologic symptoms, services received, satisfaction with treatment, communication with providers, and informational needs. Survey responses were obtained from 309 women with breast cancer, with a mean age of 56 years and high level of education. RESULTS: Results revealed that most breast cancer survivors have significant needs for CAM services, and yet only a small proportion actually receives them. For example, virtually all women reported symptoms potentially amenable to treatment via individual counseling or nutritional interventions; however, only 29% and 45%, respectively, received such services. Women who did and those who did not receive CAM services (e.g., counseling, massage, meditation, and supplementation) generally did not differ in terms of their need for such services as measured via symptoms that could be supported by these interventions. However, the majority failed to be referred for such treatments or were unable to access them if referred. CONCLUSIONS: Results suggest that while access to services played a small role in nonreceipt of CAM services, the largest reason for CAM nonreceipt was failure to recognize their potential benefit on the part of providers and at least some patients. Raising awareness about the potential value of CAM among care providers for women with breast cancer is crucial, as it will likely lead to more CAM acceptance and utilization. Once providers accept and refer for CAM, patients' quality of life may be considerably enhanced, as the extant literature has demonstrated the potential value of CAM for breast cancer survivors.

Mesophilic and Thermophilic Cultures Used in Traditional Cheesemaking.

Most cheese varieties require acidification of milk by a select group of bacteria called starters. They ferment lactose to lactic acid and in so doing aid the cheesemaker in developing the desired texture as well as acidity of the cheese. However, while other microorganisms play the major role in flavor development of cheese, it is the starter that sets the stage for quality cheese manufacture. Starters were traditionally derived from the native microflora of the milk, but this practice is almost unheard of today. With the advent of better hygienic milking practices and industrialized cheesemaking, there was a need for more uniformity and reliable sources of the starter culture. Today's starters are produced by companies specializing in their production as well as in the development of new strains for cheesemakers. The choice of starter for the manufacture of a specific cheese is dictated by the cheesemaking protocol, but it is also governed by the need to produce cheese with desired physical attributes. The properties of the starter that make it possible to do so help drive innovation in developing new potential choices in starter cultures. Indeed, the demands for predictable and reliable rates and extent of acidification of milk for cheesemaking and flavor development are as key for successful cheesemaking today with artisanal cheesemakers as they are for larger, more industrial-scale cheesemakers.