Aproximación a la distribución de los costos directos de la diabetes tipo 2 en Colombia.

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Electronic Transport Properties in GaAs/AlGaAs and InSe/InP Finite Superlattices under the Effect of a Non-Resonant Intense Laser Field and Considering Geometric Modifications.

In this work, a finite periodic superlattice is studied, analyzing the probability of electronic transmission for two types of semiconductor heterostructures, GaAs/AlGaAs and InSe/InP. The changes in the maxima of the quasistationary states for both materials are discussed, making variations in the number of periods of the superlattice and its shape by means of geometric parameters. The effect of a non-resonant intense laser field has been included in the system to analyze the changes in the electronic transport properties by means of the Landauer formalism. It is found that the highest tunneling current is given for the GaAs-based compared to the InSe-based system and that the intense laser field improves the current-voltage characteristics generating higher current peaks, maintaining a negative differential resistance (NDR) effect, both with and without laser field for both materials and this fact allows to tune the magnitude of the current peak with the external field and therefore extend the range of operation for multiple applications. Finally, the power of the system is discussed for different bias voltages as a function of the chemical potential.

Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica.

OBJECTIVE: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the LDLR. True HoFH due to LDLR variants had higher total (P=0.015) and LDL (low-density lipoprotein)-cholesterol (P=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (P=0.051) and had a greater frequency of xanthomas (P=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with LDLR variants. Children who are true HoFH had higher frequency of major cardiovascular events (P=0.02), coronary heart (P=0.013), and aortic/supra-aortic valve diseases (P=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of LDLR variant. From 118 subjects with LDLR variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 LDLR variants, those with at least one null allele were younger (P=0.003) and had a greater frequency of major cardiovascular events (P=0.038) occurring at an earlier age (P=0.001). CONCLUSIONS: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.

Anticancer potential of new 3-nitroaryl-6-(N-methyl)piperazin-1,2,4-triazolo[3,4-a]phthalazines targeting voltage-gated K+ channel: Copper-catalyzed one-pot synthesis from 4-chloro-1-phthalazinyl-arylhydrazones.

A series of six 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines were prepared through a facile and efficient one-pot copper-catalyzed procedure from 4-chloro-1-phthalazinyl-arylhydrazones with relatively good yields (62-83%). The one-pot copper-catalytic procedure consists of two simultaneous reactions: (i) a direct intramolecular dehydrogentaive cyclization between ylidenic carbon and adjacent pyrazine nitrogen to form 1,2,4-triazolo ring and, (ii) a direct N-amination on carbon-chlorine bond. Then, an in vitro anticancer evaluation was performed for the synthesized compounds against five selected human cancer cells (A549, MCF-7, SKBr3, PC-3 and HeLa). The nitro-derivatives were significantly more active against cancer strains than against the rest of tested compounds. Specifically, compound 8d was identified as the most promising anticancer agent with significant biological responses and low relative toxicities on human dermis fibroblast. The cytotoxic effect of compound 8d was more significant on PC3, MCF-7 and SKBr3 cancer cells with low-micromolar IC50 value ranging from 0.11 to 0.59 µM, superior to Adriamycin drug. Mechanistic experimental and theoretical studies demonstrated that compounds 8d act as a K+ channel inhibitor in cancer models. Further molecular docking studies suggest that the EGFR Tyrosine Kinase enzyme may be a potential target for the most active 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines.

Prognostic impact of renal failure recovery in patients with newly diagnosed multiple mieloma.

Background Renal failure (RF) is a common complication in patients with newly diagnosed multiple myeloma (NDMM). Aim To evaluate the frequency of RF in NDMM patients, and the prognostic impact of its reversibility. Material and Methods A retrospective study evaluating demographic and clinical characteristics of 154 consecutive patients with NDMM was carried out. Estimated glomerular filtration rate (eGFR) was calculated at the beginning and at the end of the induction therapy. In addition, we evaluated renal responses (RR) according to the International Myeloma Working Group (IMWG) criteria. The induction regimen was based on thalidomide in all cases. Results Fifty-three patients had RF (34.4%). Complete renal response (RR) was achieved in 51%. Three years overall survival in patients without RF, with RF and complete RR, and patients with RF and any other RR, was 66, 47 and 13%, respectively. Median survival was 53, 27 and 6 months, respectively (p < 0.01). In the multivariate analysis, RF and hypercalcemia were independent predictors of a worse outcome. Conclusions Achieving a complete RR in patients with NDMM, is associated with a better survival.

1 Gb/s chaotic encoded W-band wireless transmission for physical layer data confidentiality in radio-over-fiber systems.

Physical layer encryption methods are emerging as effective, low-latency approaches to ensure data confidentiality in wireless networks. The use of chaotic signals for data masking is a potential solution to prevent a possible eavesdropper to distinguish between noise and sensitive data. In this work, we experimentally demonstrate the W-band wireless transmission of a 1 Gb/s chaotic signal over 2 m in a radio-over-fiber architecture. The chaos encoding scheme is based on the transition between different states of a Duffing oscillator system, digitally implemented. The bit error rate achieved in all cases was below the forward error correction limit for 7 % overhead. The presented results validate the proposed chaos-based physical layer encoding solution for gigabit data transmissions in hybrid millimeter-wave/photonic networks.

Higher pharmaceutical public expenditure after direct price control: improved access or induced demand? The Colombian case.

BACKGROUND: High pharmaceutical expenditure is one of the main concerns for policymakers worldwide. In Colombia, a middle-income country, outpatient prescription represents over 10% of total health expenditure in the mandatory benefits package (POS), and close to 90% in the complementary government fund (No POS). In order to control expenditure, since 2011, the Ministry of Health introduced price caps on inpatient drugs reimbursements by active ingredient. By 2013, more than 400 different products, covering 80% of public pharmaceutical expenditure were controlled. This paper investigates the effects of the Colombian policy efforts to control expenditure by controlling prices. METHODS: Using SISMED data, the official database for prices and quantities sold in the domestic market, we estimate a Laspeyres price index for 90 relevant markets in the period 2011-2015, and, then, we estimate real pharmaceutical expenditure. RESULTS: Results show that, after direct price controls were enacted, price inflation decreased almost - 43%, but real pharmaceutical expenditure almost doubled due mainly to an increase in units sold. Such disproportionate increase in units sold maybe attributable to better access to drugs due to lower prices, and/or to an increase in marketing efforts by the pharmaceutical industry to maintain profits. CONCLUSIONS: We conclude that pricing interventions should be implemented along with a strong market monitoring to prevent market distortions such as inappropriate and unnecessary drug use.

BCG: A throwback from the stone age of vaccines opened the path for bladder cancer immunotherapy.

INTRODUCTION: It is 40 years since the initial documentation of the efficacy of bacille Calmette-Guérin (BCG) in the management of non-muscle invasive bladder cancer (NMIBC) and probably an opportune a time as any to retrace the origins of this development and to reflect on the progress that has occurred on the use of immune modifiers in the treatment of NMIBC. MATERIALS AND METHODS: A PubMed search for publications on the history of BCG was conducted, and those related to the development of the vaccine for protection against tuberculosis as well as those published in the last 40 years related to its use for treatment for NMIBC were selected for review. A manual search was also carried out for recent articles on immunotherapy for NMIBC failing to respond to BCG. Publications were selected for their usefulness in exemplifying the development of BCG as an antineoplastic agent, elucidating its mechanisms of action of BCG or introducing significant modifications in treatment regimens resulting in enhancement of its efficacy. Alternative innovative immunotherapeutic approaches were chosen to illustrate current trends in the management of this disease. RESULTS: Well thought-out modifications of the original protocol resulted in enhanced efficacy of the vaccine, which currently ranks as the best-known and most-used and investigated agent for high risk NMIBC. Despite its efficacy, a considerable number (30%-40%) of these tumors fail to respond to BCG. In addition, as a live bacterium it carries the potential for serious adverse effects and some patients are unable to tolerate it. These shortcomings have created the need for new agents. These range from other mycobacteria and viruses to monoclonal antibodies alone or in combination with other agents currently at various stages of development. CONCLUSION: After 4 decades of use, BCG remains the most effective agent against high risk NMIBC, but it still holds substantial drawbacks. The enduring use of immunotherapy for NMIBC has created a propitious environment to search for better alternatives. There are an increasing number of promising in vitro, animal and early human clinical trials to anticipate a significant therapeutic alternative in the foreseeable future.

Metodologías para la priorización en investigación en salud: una revisión sistemática de la literatura.

OBJETIVO: Identificar elementos metodológicos clave para la priorización en investigación en salud, a partir de las metodologías reportadas en la literatura científica. MÉTODOS: Se realizó una búsqueda sistemática en Medline, Embase, LILACS, y fuentes complementarias de literatura gris. Se utilizaron las palabras clave: research, methods y health priorities, en combinación con términos libres. Dos revisores independientes, de acuerdo con criterios previamente definidos, seleccionaron revisiones de la literatura o documentos metodológicos que presentaran metodologías para priorización en investigación en salud. Se extrajeron las principales características de las metodologías reportadas y se identificaron elementos comunes. RESULTADOS: Se incluyeron siete revisiones y cinco documentos metodológicos, que reportaron cuatro metodologías estructuradas específicas y múltiples aproximaciones metodológicas que combinan elementos diversos. En general, estas metodologías integran la perspectiva de actores clave con información objetiva, mediante la aplicación de técnicas estandarizadas de participación, para establecer un ranking de prioridades, con base en criterios previamente definidos. Se identificaron elementos metodológicos comunes relacionados con pasos del proceso, mecanismos de participación, criterios para priorizar y análisis de resultados. CONCLUSIÓN: La priorización en investigación en salud requiere el empleo de una metodología definida a priori, que debe contener como mínimo cuatro elementos clave: pasos claros del proceso, criterios para priorizar, técnicas formales de participación y métodos de análisis de resultados. Estos elementos deben ajustarse a las condiciones y necesidades del contexto de aplicación.

[The debate on regulating biotechnology drugs: Colombia in the international context]. / El debate de la regulación de medicamentos biotecnológicos: Colombia en el contexto internacional.

In September 2014, Colombia issued standards for the evaluation of biological drugs within the framework of the marketing authorization process. The Colombian approach explicitly includes a fast track for evaluating competing biologicals, which caused great national and international controversy. This article explains the context that justifies the need for this fast-track approach, critically analyzes comparability as a paradigm for the evaluation of biogenerics, and shows that Colombia's position is not isolated and is based on global regulatory trends.

[Survival of older patients starting hemodialysis in Chile]. / Análisis de sobrevida en pacientes de edad avanzada que inician hemodiálisis crónica en Servicio de Salud Chileno.

UNLABELLED: The proportion of older people with end stage renal disease is increasing. Their prognosis is characterized by a high mortality and poor quality of life. AIM: To analyze the survival of patients starting chronic hemodialysis (CHD) according to their age. MATERIAL AND METHODS: Patients admitted to CHD in the East Metropolitan Health Service of Santiago in a 2-year period were analyzed. Four age groups were created, separating patients older than 70 years in a special group. RESULTS: During the study period, 459 patients were admitted to CHD and were followed for an average of 27 months. The frequency of cardiovascular comorbidity, cancer, and chronic renal disease of unknown cause (attributed to nephrosclerosis) increased along with age. Mortality was higher at older ages. There was a significant association between starting CHD with a catheter, Charlson comorbidity index and increasing age with mortality. For those aged over 80 years, mortality at three months and one year was 25 and 43% respectively. CONCLUSIONS: Age, Charlson index and vascular access are predictors of mortality in older adults entering hemodialysis. This study suggests the importance of considering comorbidities, assessment by specialists and creating an arteriovenous fistula in this age group.

Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin.

PURPOSE: Patients with high risk recurrences after bacillus Calmette-Guérin failure have limited options. We performed an open label study to evaluate the efficacy and safety of intravesical MCNA in this setting. MATERIALS AND METHODS: Patients were treated intravesically with 8 mg MCNA weekly for 6 weeks followed by 3 weekly instillations at months 3, 6, 12, 18 and 24. Cystoscopy and cytology were performed every 3 months for 2 years with mandatory biopsy at 6 months and as clinically indicated thereafter. The primary efficacy end point was the disease-free survival rate at 1 year. RESULTS: A total of 129 patients were enrolled in study, including 91 with carcinoma in situ with or without papillary disease and 38 with papillary only tumors. Most patients had high risk disease. A total of 107 cases were bacillus Calmette-Guérin refractory and 2 or more prior bacillus Calmette-Guérin induction courses had been given in 68. Median followup in all patients was 34.7 months. The overall disease-free survival rate was 25.0% at 1 year and 19.0% at 2 years. In patients with papillary only tumors the disease-free survival rate was 35.1% and 32.2% at 1 and 2 years, respectively. The median disease-free duration in the 30 responders was 32.7 months. The progression-free survival rate was 87.3%, 79.8% and 77.7% at 1, 2 and 3 years, respectively, with a progression event in 28 patients. MCNA was well tolerated and few adverse events led to treatment discontinuation. CONCLUSIONS: Intravesical MCNA achieved significant activity in patients at high risk with nonmuscle invasive bladder cancer in whom bacillus Calmette-Guérin treatment failed, especially those with papillary only tumors and those with bacillus Calmette-Guérin relapse. A durable response was seen, particularly in patients with a response at 1 year. MCNA offers an option for patients who are not candidates for or who refuse cystectomy.

A 6-month observational study of energy, sexual desire, and body proportions in hypogonadal men treated with a testosterone 1% gel.

AIMS AND METHODS: This was a 6-month, open label, multinational, observational study in hypogonadal men treated with daily titrated dose of 50, 75, or 100 mg 1% testosterone gel (AndroGel®) in community practice. Primary outcome was effect of treatment on hypogonadal symptoms and quality of life as assessed by Aging Males' Symptoms (AMS) scale. Secondary objectives included erectile dysfunction (International Index of Erectile Function [IIEF]), fatigue (Multidimensional Fatigue Inventory [MFI]), and surrogates for body composition (waist circumference, body mass index [BMI]). RESULTS: Seven hundred and ninety-nine of the 1053 men enrolled had follow-up data at 6 months, 81.2% had ≥1 testosterone value in the normal range during the study. Substantial and significant improvements were observed in mean AMS score (-29%), IIEF score (+115.7%), and MFI scores (-21.5%). Further beneficial effects were significant decreases in mean BMI (-0.8 kg/m(2)) and waist circumference (-3.3 cm). Younger age quartiles showed greater improvements in AMS, MFI, BMI, and waist circumference than older quartiles. IIEF scores, however, did not differ significantly by age category. CONCLUSIONS: Substantial improvements in hypogonadal symptoms, quality of life, fatigue, erectile dysfunction, and libido/sexual desire were observed. Adverse drug reactions were experienced by 7.5% of the safety population over the 6-month study period.

Population-based patterns of prescription androgen use, 1976-2008.

PURPOSE: Prescription testosterone (T) has limited approved medical indications and is a controlled substance in Canada. Utilization studies in other Westernized countries have revealed sharp increases in T use in recent years. We examined medical use of androgens, including T, over a ≥30-year period among adult (18+) men in a population-based study set in a Canadian juridisdiction of universal health care. METHODS: Analyses were based on data from electronic records of dispensed prescriptions during 1976-2008 in Saskatchewan, Canada. All formulations of androgens listed in the provincial formulary (oral and injectable) were included. We examined demographics of users, androgen types used, switching patterns, and trends in the annual rate of use over time. RESULTS: There were 11 521 androgen users who were followed for an average of 11.8 years. Overall, 11 types of androgens were used, and there were 86 812 dispensing events. The mean age at first use was 56.4 years (median: 58). Men had 7.5 prescription dispensing events on average (median: 2). The most commonly used formulations were methyl-T (36.2% of users) followed by T-enanthate (32.5%), T-cypionate (22.3%), and T-undecanoate (20.0%). Most users (82%) did not switch among androgen types. The annual rate of use varied substantially over time, with a marked increase observed from 1994 to 1999 and a decrease from 2000 to 2008. CONCLUSIONS: Androgen users were largely middle aged and had relatively few dispensings. We hypothesize that observed secular trends in androgen use may align with drug treatment pattern changes for erectile dysfunction, including the advent of phosphodiesterase type 5 inhibitors.

[Ovarian stimulation with gonadotropins: comparison between recombinant FSH plus menotropins versus recombinant FSH + LH]. / Estimulación ovárica con gonadotrofinas: comparación entre un protocolo con FSH recombinante más menotropinas y un esquema con FSH más LH recombinantes.

BACKGROUND: Nowadays various assisted reproduction ovarian stimulation schemes are used for different clinical outcomes is interesting to compare. OBJECTIVE: Compare two ovarian stimulation protocols: recombinant FSH + LH versus recombinant FSH + Menotropins. MATERIAL AND METHODS: Observational, retrospective study, 38 cycles were analyzed, made from 2010 until 2013, assigned to two groups (n = 19 each), group 1 received FSHr + LHr, group 2 received FSHr + menotropins. Study variables were: days of ovarian stimulation, total gonadotropin dose, retrieved oocytes, fertilization rate, pregnancy rate and number of vitrified embryos. RESULTS: Fewer stimulation days (8.5 +/- 1.5 vs 9 +/- 1.1) were found in group 1 (recombinant gonadotropins). Group 2 (FSHr + Menotropins), had a greater total dose of gonadotropins (1930.2 +/- 346.2 vs 2000 +/- 418.8) and more retrieved oocytes (8.15 +/- 3.9 vs 8.57 +/- 4). Group 1 patients had higher pregnancy and fertilization rates (56.2 vs 36.8%, and 75.4 vs 69.3%) respectively, no statistical significance was found. CONCLUSION: This study found higher pregnancy and fertilization rates in patients treated with recombinant gonadotropins (FSH + LH) for ovarian stimulation.

CLINICAL AND SURGICAL DILEMMAS IN OCTOGENARIAN PATIENTS WITH SMALL BOWEL OBSTRUCTION.

BACKGROUND: Small bowel obstruction (SBO) is a major problem in emergencies. Comorbidities increase morbimortality, which is reflected in higher costs. There is a lack of Latin American evidence comparing the differences in postoperative results and costs associated with SBO management. AIMS: To compare the risk of surgical morbimortality and costs of SBO surgery treatment in patients older and younger than 80 years. METHODS: Retrospective analysis of patients diagnosed with SBO at the University of Chile Clinic Hospital from January 2014 to December 2017. Patients with any medical treatment were excluded. Parametric statistics were used (a 5% error was considered statistically significant, with a 95% confidence interval). RESULTS: A total of 218 patients were included, of which 18.8% aged 80 years and older. There were no differences in comorbidities between octogenarians and non-octogenarians. The most frequent etiologies were adhesions, hernias, and tumors. In octogenarian patients, there were significantly more complications (46.3 vs. 24.3%, p=0.007, p<0.050). There were no statistically significant differences in terms of surgical complications: 9.6% in <80 years and 14.6% in octogenarians (p=0.390, p>0.050). In medical complications, a statistically significant difference was evidenced with 22.5% in <80 years vs 39.0% in octogenarians (p=0.040, p<0.050). There were 20 reoperated patients: 30% octogenarians and 70% non-octogenarians without statistically significant differences (p=0.220, p>0.050). Regarding hospital stay, the average was significantly higher in octogenarians (17.4 vs. 11.0 days; p=0.005, p<0.050), and so were the costs, being USD 9,555 vs. USD 4,214 (p=0.013, p<0.050). CONCLUSIONS: Patients aged 80 years and older with surgical SBO treatment have a higher risk of medical complications, length of hospital stay, and associated costs compared to those younger.

Bacillus Calmette-Guérin immunotherapy for genitourinary cancer.

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The administration of Bacillus Calmette-Guérin (BCG) immunotherapy has become the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) and carcinoma in-situ (CIS) in terms of prevention of recurrence and progression. While most agree on a 6 week induction cycle, various maintenance schedules (if any at all) have been implemented without a unifying consensus. This review assesses the historical emergence of BCG immunotherapy, beginning with its discovery as a vaccinatin for tuberculosis to its effect on the host immune system and potential therapeutic benefits for various oncologic conditions. The data establishing BCG immunotherapy as the standard of care for high-grade NMIBC and CIS over other bladder instillation modalities is presented in addition to the effect maintenance BCG therapy has on sustaining the immuno-protective effect. Bacillus Calmette-Guérin (BCG) immunotherapy is currently the most effective treatment of non-muscle invasive bladder cancer and one of the most successful applications of immunotherapy to the treatment of cancer. This review summarises the history and development of BCG as a modern cancer treatment, appraises current optimal application of BCG immunotherapy in bladder cancer, discusses promising new therapies closely related to BCG, and briefly explores the possibility that BCG or related treatments may have an application in other urological malignancies. BCG is a nonspecific stimulant to the reticuloendothelial system and induces a local inflammatory response with the infiltration of granulocytes followed by macrophages and lymphocytes, particularly helper T cells. The initial BCG controlled trial showed a statistically significant reduction in tumour recurrence and found the advantage increased with duration of follow-up. Similar results were reported in much higher risk patients in an independent concurrent study. Follow-up suggested that a single 6-week course of intravesical BCG provided long-term protection (up to 10 years) from tumour recurrence and even reduced disease progression. While induction BCG (six weekly instillations) reduced recurrence, progression and mortality at 10 years, this advantage was lost by 15 years, and patients remained at high risk for progression without the use of maintenance BCG. In a meta-analysis by the Cochrane group, induction BCG was found to be markedly superior to mitomycin C in high-risk patients but not in low-risk patients. Additionally, the National Comprehensive Cancer Network guidelines lists the use of intravesical BCG as preferred therapy, citing Category 1 data for high-grade Ta, all T1, and any Tis tumours. Maintenance BCG therapy may be the most important advance in BCG treatment of bladder cancer since the initial introduction. The risk of tumour recurrence and disease progression is life-long in most patients, but the immune stimulation induced by BCG wanes with time. Logarithmic dose reduction of BCG in patients with increasing side-effects will typically prevent escalation of toxicity. Simple dose reduction, appropriate antibiotics, and understanding treatment contraindications have greatly increased the safety of BCG. The 3-week maintenance schedule for 3 years has been evaluated in randomised clinical trials and appears to be the current optimal treatment. With the success achieved in bladder cancer and the relative safety and economy of BCG, consideration should be given to further research for its effectiveness in other genitourinary malignancies.

The long and tortuous history of the discovery of testosterone and its clinical application.

INTRODUCTION: The testis importance in homeostasis was recognized for millennia, but a consistent interest in exploring their endocrine function only goes back to about a century. AIM: The aim of this study is to provide a succinct perspective of the events leading to the discovery of testosterone, the mind-boggling early attempts at therapy and today's situation. METHOD: The literature was reviewed with searches in OvidSP Medline, PubMed, and Google Scholar under the headings of testosterone/androgens history. Due to the explosion of reports between the late 19th and early 20th centuries, a manual review of the collection of the period's journals at the university's library was performed. Pertinent books were consulted for specific biographical details. RESULTS: There is a robust body of literature dealing with testicular function for the period starting in the late 1800s. It is illustrative to learn the painful efforts of many well-intentioned and honest scientists with more conviction and determination than knowledge. Among them, unfortunately, a number of charlatans and profiteers tainted the concept of hypogonadism and its treatment with repercussions lasting until this day. The discovery and synthesis of testosterone represent the effort of brilliant minds (two Nobel Prizes) in various countries and frequently working for the pharmaceutical industry. Shortly after testosterone became available, controversy arose about its application, use, abuse, and potential detrimental effects. Over the decades, the hullabaloo about hypogonadism and its treatment has focused on a variety of issues ranging from absurd efficacy claims to solid studies and from doubts of its existence to convincing proof of a detrimental age-associated deficit in testosterone production. CONCLUSIONS: The history of testosterone discovery, synthesis, and introduction into the therapeutic armamentarium is an outstanding example of human curiosity, ingenuity, greed, and skepticism. Despite the vast progress in the field, many issues remain unresolved, but thoughtful science augurs well for its future.

Adapting to context in community-based participatory research: "participatory starting points" in a Chinese immigrant worker community.

Community-based participatory research (CBPR) is increasingly being used to better understand and improve the health of diverse communities. A key strength of this research orientation is its adaptability to community contexts and characteristics. To date, however, few studies explicitly discuss adaptations made to CBPR principles and processes in response to community context and partners' needs. Using data from our CBPR study, the San Francisco Chinatown Restaurant Worker Health and Safety Project, and drawing from literature on immigrant political incorporation, we examine the links between the contexts of the Chinese immigrant worker community, adaptations made by our collaborative, and study outcomes. In particular, we explore the concepts of contexts of reception and participatory starting points, which may be especially relevant for partnerships with immigrant communities whose members have historically had lower rates of civic and political participation in the US. We discuss contextual findings such as worker partner accounts of language barriers, economic and social marginalization, and civic skills and participation, as well as subsequent adaptations made by the partnership. We also describe the relative effectiveness of these adaptations in yielding equitable participation and building partners' capacity. We conclude by sharing lessons learned and their implications for CBPR and partnerships with immigrant communities more broadly.