CD8+ tissue-resident memory T-cell development depends on infection-matching regulatory T-cell types.

Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8+ memory T cells develop at the location of infection: tissue-resident memory T cells (TRM). CD8+ T-cell responses are associated with type-1 infections and type-1 regulatory T cells (TREG) are important for CD8+ T-cell development, however, if CD8+ TRM cells develop under other infection types and require immune type-specific TREG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8+ TRM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching TREG population contributing transforming growth factor-ß. Nevertheless, type-1 TREG cells remain the most important population for TRM cell development. Once established, TRM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8+ TRM cells.

Lymphoma Presenting as a Soft Tissue Mass.

Teaching Point: Lymphomatous involvement of the skeletal muscle is rare; however, because lymphoma can be treated with chemotherapy, it is crucial to consider it in the differential diagnosis of a soft tissue mass in the appropriate clinical and imaging setting.

The Hollow Adrenal Gland Sign: An Ominous Alert.

Teaching Point: The hollow adrenal gland sign is common, and may be specific, in patients with septic shock, and is a predictor of poor prognosis.

Incidental Ureteroinguinal Hernia in a Patient With a Single Kidney.

Teaching point: An ureteroinguinal hernia is a very rare diagnosis with typical radiological findings that must be reported, particularly in surgical candidates.

Inflammatory and nutritional biomarkers as predictors of non-resectability and early recurrence in pancreatic and periampullary cancer.

BACKGROUND: Some pancreatic tumors considered resectable on the preoperative staging are unresectable during surgical exploration. Moreover, some patients subjected to tumor resection have an early recurrence. METHODS: Patients with pancreatic or periampullary carcinoma diagnosed between January 2005 and August 2017 at the Prof. Doutor Fernando Fonseca Hospital were retrospectively analyzed. Biochemical and radiological inflammatory biomarkers were compared according to disease staging at diagnosis, intraoperative staging and early recurrence (<6 months). RESULTS: Three hundred ninety-one patients were included. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, C-reactive-protein-to-albuminemia ratio (CRP/ALB), Prognostic Nutritional Index, modified Glasgow Prognostic Score and CA19-9 were associated with metastatic disease at diagnosis. NLR, CRP/ALB, mGPS and CA19-9 were independent predictors of disease staging at diagnosis on multivariate analysis. One hundred eight patients underwent surgery, of which 23.8% were found to have unresectable disease at intra-operative staging. 26.9% had early disease recurrence. CRP/ALB and CA19-9 were significantly higher in patients with evidence of disease at 6 months postoperatively. Computed tomography sarcopenia index HUAC was significantly lower in patients with evidence of disease at 6 months postoperatively. When adjusted for histology, none of the biomarkers were independent predictors of unresectable disease or early recurrence. CONCLUSIONS: NLR, CRP/ALB, mGPS and CA19-9 at diagnosis were predictors of disease staging with low performance. Preoperative inflammatory biomarkers were not predictors of unresectable disease or early recurrence.

Type 1 Treg cells promote the generation of CD8+ tissue-resident memory T cells.

Tissue-resident memory T (TRM) cells, functionally distinct from circulating memory T cells, have a critical role in protective immunity in tissues, are more efficacious when elicited after vaccination and yield more effective antitumor immunity, yet the signals that direct development of TRM cells are incompletely understood. Here we show that type 1 regulatory T (Treg) cells, which express the transcription factor T-bet, promote the generation of CD8+ TRM cells. The absence of T-bet-expressing type 1 Treg cells reduces the presence of TRM cells in multiple tissues and increases pathogen burden upon infectious challenge. Using infection models, we show that type 1 Treg cells are specifically recruited to local inflammatory sites via the chemokine receptor CXCR3. Close proximity with effector CD8+ T cells and Treg cell expression of integrin-ß8 endows the bioavailability of transforming growth factor-ß in the microenvironment, thereby promoting the generation of CD8+ TRM cells.

What you should know about emphysematous vaginitis?

Emphysematous vaginitis represents a rare and self-limited condition, which presents with vaginal discharge. Despite its benignity, it has some worrisome imaging features, which should be recognized in order to avoid unnecessary invasive procedures.

Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes.

Epithelial-resident T lymphocytes, such as intraepithelial lymphocytes (IELs) located at the intestinal barrier, can offer swift protection against invading pathogens. Lymphocyte activation is strictly regulated because of its potential harmful nature and metabolic cost, and most lymphocytes are maintained in a quiescent state. However, IELs are kept in a heightened state of activation resembling effector T cells but without cytokine production or clonal proliferation. We show that this controlled activation state correlates with alterations in the IEL mitochondrial membrane, especially the cardiolipin composition. Upon inflammation, the cardiolipin composition is altered to support IEL proliferation and effector function. Furthermore, we show that cardiolipin makeup can particularly restrict swift IEL proliferation and effector functions, reducing microbial containment capability. These findings uncover an alternative mechanism to control cellular activity, special to epithelial-resident T cells, and a novel role for mitochondria, maintaining cells in a metabolically poised state while enabling rapid progression to full functionality.

Urachal Adenocarcinoma: A Case Report with Key Imaging Findings and Radiologic-Pathologic Correlation.

Urachal pathologies are rare and can mimic numerous abdominal and pelvic diseases. Differential diagnosis of urachal anomalies can be narrowed down by proper assessment of lesion location, morphology, imaging findings, patient demographics, and clinical history. We report a case of a 60-year-old male, with a history of unintentional weight loss without associated symptoms, who was diagnosed with locally invasive urachal adenocarcinoma. With this article, we pretend to emphasize urachal adenocarcinoma clinical features along with its key imaging findings with radiologic-pathologic correlation.

Caracterização epidemiológica de uma clinica foniátrica / Epidemiological characterization of a phoniatric clinical practice / Caracterización epidemiológica de una clínica foniátrica

Introdução: Os distúrbios de linguagem convocam profissionais de diferentes campos de conhecimento a refletirem sobre os casos atendidos e seus enigmas. Neste contexto, a possibilidade de diálogo com outras áreas pode responder sobre o atendimento clínico nesse campo, com a finalidade de pensar a direção do tratamento. Dados epidemiológicos também podem contribuir com informações clínicas para a condução dos pacientes. Objetivo: Caracterizar epidemiologicamente uma clínica foniátrica considerando os processos de diagnóstico e conduta. Método: Estudo retrospectivo de coorte histórica com corte transversal. De um total de 879 prontuários de pacientes com queixa de dificuldades na comunicação submetidos à avaliação foniátrica, em uma clínica particular. Resultados: O gênero masculino foi prevalente (64,5%), o distúrbio de linguagem de etiologia multifatorial foi o mais frequente (44%) e a conduta comumente adotada foi a terapia fonoaudiológica. Conclusão: O Fonoaudiólogo destaca-se como o profissional que mais encaminha pacientes para avaliação foniátrica e é o que mais recebe indicações de pacientes a partir da conduta do foniatra, declarando que a parceria entre essas especialidades, a Fonoaudiologia e a Foniatria, pode contribuir para a evolução dos tratamentos desses pacientes. Destacamos, ainda, a importância do psicólogo na composição da equipe interdisciplinar no atendimento aos pacientes com distúrbios da comunicação, pois nos resultados esta foi a segunda especialidade que recebeu mais encaminhamentos do foniatra, considerando que alterações e sofrimentos psíquicos estão diretamente relacionados com os problemas de linguagem.

Introduction: Child development disorders invite people from different fields of knowledge to reflect on their roles. Within this context, the practice of speech therapy causes continuous reflections based on the singularity of treated cases and their riddles. As a path, the possibility of a dialogue with other areas can respond to clinical possibilities in this field, in order to think about the direction of treatment. Epidemiologic data can also contribute to clinical information for patients' management. Objective: To characterize epidemiologically a phoniatric clinical practice considering the processes of diagnosis and management. Method: Retrospective study of historical cohort with cross-sections. A total of 879 records of patients with difficulties in communicating complaints submitted to phoniatric evaluation at a private clinic. Results: The male gender was prevalent (64.5%), the language disorder of multifactorial etiology was the most frequent (44%) and the treatment commonly adopted was speech therapy. Interdisciplinary work was the discussion of diagnosis and treatment. Conclusion: Speech therapist stands out as a professional that directs more patients to phoniatric evaluation and is the one which most receives indications of patients from the conduct of the Phoniatrist, stating that the partnership between these specialties, Speech Therapy and Phoniatrics, can contribute to the development of treatments for these patients. We also highlight the importance of the psychologist in the composition of the interdisciplinary team in serving patients with communication disorders, because the results show that it was the second specialty that received more referrals from the Phoniatrist, considering that changes and mental suffering are directly related to language problems.

Introducción: Los trastornos del lenguaje convocan profesionales de diferentes campos del conocimiento para reflexionar sobre los casos atendidos y sus enigmas. En ese contexto, la posibilidad de diálogo con otras áreas puede responder sobre el atendimineto clínico en este campo, para pensar sobre la dirección del tratamiento. Los datos epidemiológicos también pueden contribuir con informaciones clinicas para el tratamiento de los pacientes. Objetivo: Caracterizar epidemiológicamente una clínica foniátrica considerando los procesos de diagnóstico y conduta. Método: Estudio retrospectivo de cohorte histórica con secciones transversales. Un total de 879 archivos de pacientes con quejas de dificultades en la comunicación sometidos a la evaluación foniátrica en una clínica privada. Resultados: El género masculino fué prevalente (64,5%), el distúrbio de lenguaje de etiología multifactorial fue la más fercuente (44%) y la conducta comúnmente adoptada fue la terapia fonoaudiológica. Conclusión: el fonoaudiologo se destaca como profesional que dirige más pacientes a la evaluación foniátrica y es el que mas recibe indicaciones de pacientes del médico foniatra. La asociación entre estas especialidades, Fonoaudiología y Foniatría, puede contribuir para el desarrollo del tratamientos de los para estos pacientes. También destacamos la importancia del psicólogo en la composición del equipo interdisciplinario en el servicio a los pacientes con trastornos de la comunicación, ya que en los resultados fue la segunda especialidad que recibió más referencias foniatra teniendo en cuenta que los cambios y el sufrimiento mental están directamente relacionados con problemas de lenguaje.

Epidemiology of communication disorders in childhood phoniatric clinical practice / Epidemiologia dos distúrbios de comunicação na infância em clínica foniátrica

INTRODUCTION: Language acquisition and development require an understanding of physical and psychosocial aspects during diagnosis and treatment. At this point, a partnership between phoniatric physicians and other health professionals is often a determinant for favorable prognosis.OBJECTIVE: To identify the clinical and epidemiological characteristics of a pediatric population attending a phoniatric clinical practice.METHODS: Study design: Cross-sectional cohort. Retrospective, epidemiological study of 297 children, seen in phoniatric appointments between 1976 and 2005. Outcome variables were referral origin, gender, age, mean age, diagnosis, and treatment approach.RESULTS: 66% were male and 34% were female, with a mean age of 6.4 years. The largest number of referrals for phoniatric treatments came from speech therapists (38%). The predominant complaint was alteration in speech (35%); the diagnostics in speech, language, and fluency (49.5%) are noteworthy. Considering the total of the patients analyzed, 28.2% were referred for speech therapy and 11.8% for psychotherapy.CONCLUSION: The studied population is predominantly male, the diagnosis points to a higher incidence in cases of impairment in speech, language, and fluency; the most common treatment was speech therapy.

INTRODUÇÃO: Aquisição e desenvolvimento da linguagem demandam cuidados exigindo compreensão dos aspectos orgânicos e psíquicos no diagnóstico e tratamento. Assim, parceria entre foniatra e outros profissionais é, muitas vezes, determinante de um prognóstico favorável.OBJETIVO: Caracterizar clínica e epidemiologicamente os distúrbios de comunicação em crianças na prática clínica.MÉTODO: Coorte transversal histórica. Estudo epidemiológico retrospectivo de 297 prontuários de crianças atendidas em consulta foniátrica no período entre 1976 a 2005. Variáveis: origem do encaminhamento, gênero, média da idade, diagnóstico e conduta para tratamento.RESULTADOS: 66% foram do gênero masculino e 34% do feminino com média de idade de 6,4 anos. Maior número de encaminhamentos foi realizado por fonoaudiólogos (38%). A queixa predominante era de alterações na fala 35% e ressaltam-se os diagnósticos na área da fala, linguagem e fluência (49,5%). Do total destacaram-se os encaminhamentos para: 28,2% fonoterapia e 11,8% psicoterapia.CONCLUSÃO: A população atendida foi predominantemente masculina, o diagnóstico aponta maior incidência em quadros de comprometimento na fala, linguagem e fluência e o tratamento mais indicado foi fonoterapia.

Epidemiology of communication disorders in childhood phoniatric clinical practice.

INTRODUCTION: Language acquisition and development require an understanding of physical and psychosocial aspects during diagnosis and treatment. At this point, a partnership between phoniatric physicians and other health professionals is often a determinant for favorable prognosis. OBJECTIVE: To identify the clinical and epidemiological characteristics of a pediatric population attending a phoniatric clinical practice. STUDY DESIGN: Cross-sectional cohort. Retrospective, epidemiological study of 297 children, seen in phoniatric appointments between 1976 and 2005. Outcome variables were referral origin, gender, age, mean age, diagnosis, and treatment approach. RESULTS: 66% were male and 34% were female, with a mean age of 6.4 years. The largest number of referrals for phoniatric treatments came from speech therapists (38%). The predominant complaint was alteration in speech (35%); the diagnostics in speech, language, and fluency (49.5%) are noteworthy. Considering the total of the patients analyzed, 28.2% were referred for speech therapy and 11.8% for psychotherapy. CONCLUSION: The studied population is predominantly male, the diagnosis points to a higher incidence in cases of impairment in speech, language, and fluency; the most common treatment was speech therapy.

In vitro exposure to the organochlorine p,p'-DDE affects functional human sperm parameters.

Although no information exists regarding the levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) on reproductive fluids of heavily exposed populations, they are possibly quite high given the serum levels reported so far. In these populations altered semen quality has been reported, although the direct effects of this DDT metabolite on crucial sperm parameters remain largely unexplored. With this in mind, a long-term in vitro incubation that better mimics the putative continuous exposure of spermatozoa to p,p'-DDE in the female reproductive tract in vivo was used. Before compromising sperm viability, continuous p,p'-DDE exposure remarkably decreased sperm motility, possibly due to the combined reduction in the proportion of sperm with high mitochondrial membrane potential and cellular ATP levels, all of which were clearly more affected at 50 and 100 µM p,p'-DDE. Moreover, 25 µM p,p'-DDE was also able to promote a decline in sperm with high MMP, however without significantly affecting motility. On the other hand, p,p'-DDE at the highest concentration strongly inhibited the process of capacitation following 24h of incubation. In conclusion, human sperm function is affected by continuous high p,p'-DDE exposure which may ultimately compromise male fertility. Given our previously findings that showed a non-regulated Ca(2+) entry in the presence of p,p'-DDE, we suggest that this organochlorine may promote mitochondrial Ca(2+) overload which may culminate in a general mitochondrial dysfunction and cellular ATP depletion, thus affecting sperm fertilizing potential. Our findings suggest a broader understanding of the non-genomic mechanism of p,p'-DDE action in human sperm.

Atendendo irmãos na clínica fonoaudiológica ? algumas reflexões / Brothers as patients at speech therapy clinic ? reflections / Atendiendo hermanos en fonoaudiologia clínica - algunas reflexiones

O atendimento a irmãos é algo que provoca reflexões na área terapêutica. É comum uma mesma família buscar tratamento para outro filho com o profissional já conhecido com quem se construiu uma relação de confiança. Mas o fonoaudiológico clínico deve estar advertido de que os efeitos desse trabalho podem ser contrários aos esperados para o tratamento. Não é o mesmo atender irmãos na clínica médica, odontológica, na terapêutica. Algumas áreas como a da Psicologia e da Psicanálise tem isso bem definido, mas a Fonoaudiologia ainda não. Fonoaudiólogos atendem irmãos simultaneamente, o que provoca um movimento muitas vezes contraditório para o tratamento, resultando em resistência, desistência ou troca de terapeuta. Propomos discutir alguns aspectos sobre a questão do atendimento para irmãos em fonoterapia, considerando as histórias e singularidades dos sujeitos e ainda refletir quando pode, ou não, ser indicado esse tipo de atendimento a partir da transferência e do setting estabelecido em algumas experiências clínicas.(AU)(AU)

The attendance of brothers is something that has led to reflections on the speech therapy area. It is usual for a family to search treatment for another child with the professional with whom the family has built a relationship of trust. But the speech therapist must be warned that the effects of this work may not be the expected treatment. The attendance of brothers in the speech therapy area is not the same as on the medical or dental therapy. Some areas as psychology and psychoanalysis have well defined these procedures, but they have not yet been established in the speech therapy area. Speech therapy professionals attend brothers simultaneously, causing resistance movements, withdraw or change of therapist. We propose to discuss some aspects on this issue, considering the history and uniqueness of individuals, and reflections about when this kind of attendance is indicated, beginning with the link and setting based on the experiences from clinical trials.(AU)(AU)

El tratamiento de hermanos es algo que provoca reflexiones en el área terapéutico. Es común em una misma familia que se busque tratamiento para mas de un hijo con el profesional ya conocido com quien se construyó una relación de confianza. Pero el fonoaudiólogo clínico debe estar advertido que los efectos de ese trabajo pueden ser contrarios a los esperados. No es lo mismo atender hermanos em la clínica médica, en la odontológica, y en el campo terapéutico. Algunas áreas como la de psicología y de psicoanálisis tienen eso bien definido, pero la Fonoaudiologia todavía no lo tiene. Fonoaudiólogos atienden hermanos simultáneamente lo que provoca un movimiento muchas veces contradictorio para el tratamiento, resultando en resistencia, retiro o cambio de terapeuta. Proponemos la discusión de algunos aspectos sobre el tema del tratamiento de hermanos en monoterapia, teniendo en cuenta las historias y singularidades de los sujetos y aún reflejar sobre cuando se puede o no indicar ese tipo de atención, a partir de la transferencia y del setting establecido en algunas experiencias clínicas.(AU)(AU)

Atendendo irmãos na clínica fonoaudiológica ? algumas reflexões / Brothers as patients at speech therapy clinic ? reflections / Atendiendo hermanos en fonoaudiologia clínica - algunas reflexiones

O atendimento a irmãos é algo que provoca reflexões na área terapêutica. É comum uma mesma família buscar tratamento para outro filho com o profissional já conhecido com quem se construiu uma relação de confiança. Mas o fonoaudiológico clínico deve estar advertido de que os efeitos desse trabalho podem ser contrários aos esperados para o tratamento. Não é o mesmo atender irmãos na clínica médica, odontológica, na terapêutica. Algumas áreas como a da Psicologia e da Psicanálise tem isso bem definido, mas a Fonoaudiologia ainda não. Fonoaudiólogos atendem irmãos simultaneamente, o que provoca um movimento muitas vezes contraditório para o tratamento, resultando em resistência, desistência ou troca de terapeuta. Propomos discutir alguns aspectos sobre a questão do atendimento para irmãos em fonoterapia, considerando as histórias e singularidades dos sujeitos e ainda refletir quando pode, ou não, ser indicado esse tipo de atendimento a partir da transferência e do setting estabelecido em algumas experiências clínicas...

The attendance of brothers is something that has led to reflections on the speech therapy area. It is usual for a family to search treatment for another child with the professional with whom the family has built a relationship of trust. But the speech therapist must be warned that the effects of this work may not be the expected treatment. The attendance of brothers in the speech therapy area is not the same as on the medical or dental therapy. Some areas as psychology and psychoanalysis have well defined these procedures, but they have not yet been established in the speech therapy area. Speech therapy professionals attend brothers simultaneously, causing resistance movements, withdraw or change of therapist. We propose to discuss some aspects on this issue, considering the history and uniqueness of individuals, and reflections about when this kind of attendance is indicated, beginning with the link and setting based on the experiences from clinical trials...

El tratamiento de hermanos es algo que provoca reflexiones en el área terapéutico. Es común em una misma familia que se busque tratamiento para mas de un hijo con el profesional ya conocido com quien se construyó una relación de confianza. Pero el fonoaudiólogo clínico debe estar advertido que los efectos de ese trabajo pueden ser contrarios a los esperados. No es lo mismo atender hermanos em la clínica médica, en la odontológica, y en el campo terapéutico. Algunas áreas como la de psicología y de psicoanálisis tienen eso bien definido, pero la Fonoaudiologia todavía no lo tiene. Fonoaudiólogos atienden hermanos simultáneamente lo que provoca un movimiento muchas veces contradictorio para el tratamiento, resultando en resistencia, retiro o cambio de terapeuta. Proponemos la discusión de algunos aspectos sobre el tema del tratamiento de hermanos en monoterapia, teniendo en cuenta las historias y singularidades de los sujetos y aún reflejar sobre cuando se puede o no indicar ese tipo de atención, a partir de la transferencia y del setting establecido en algunas experiencias clínicas...

In vitro effects of cationic compounds on functional human sperm parameters.

OBJECTIVE: To determine the mechanisms of spermicidal activity by cationic compounds. DESIGN: In vitro study with human sperm. SETTING: Academic research institute in collaboration with a university hospital. PATIENT(S): Normozoospermic men providing samples for routine analysis or assisted reproductive technologies. INTERVENTION(S): In vitro incubation of sperm with commercially available cationic surfactants. MAIN OUTCOME MEASURE(S): The effects of benzalkonium bromide (C12Bzk), pyridinium bromide (C12Pyr), and dodecyl trimethylammonium bromide (C12TAB) on human sperm viability, motility, mitochondrial status, capacitation, acrosomal status, and calcium movements were monitored. RESULT(S): There was a universal decrease in mitochondrial membrane potential after 180 minutes. Incubation with C12Bzk led to less capacitated sperm at LD50 after 180 minutes (46.0%) as well as to 20.2% of cells significantly increasing their intracellular calcium. C12Pyr was the stronger compound, affecting capacitation and acrosomal status at LD50 and promoting a higher calcium influx (81.7%). C12TAB increased the number of acrosome-reacted sperm at LD50 after 180 minutes and led to a significant increase in calcium signaling (61.2% and 67.9%, respectively). CONCLUSION(S): Cationic surfactants seem to impair sperm function at various levels, although C12Pyr was shown to be more effective. Given the concentrations used, these compounds are not necessarily acting as surfactants. To our knowledge, this is the first study that evaluates contraceptive compounds by monitoring sperm calcium signaling, and this seems to be a sensitive parameter in terms of determining the action of putative spermicides.

Exogenous glucose improves long-standing human sperm motility, viability, and mitochondrial function.

A relevant fraction of human sperm can be maintained in simple phosphate-buffered saline (PBS) for more than 1 week at room temperature, a time that could be doubled if glucose was available. This does not seem to be directly due to sperm mitochondrial activity.

In vitro surfactant structure-toxicity relationships: implications for surfactant use in sexually transmitted infection prophylaxis and contraception.

BACKGROUND: The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. METHODOLOGY/PRINCIPAL FINDINGS: We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants--nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (C(n)TAB (n = 10 to 16), C(12)PB, and C(12)BZK)--were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C(12)PB and C(12)BZK, does not justify their use as contraceptive agents. C(12)PB and C(12)BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. CONCLUSIONS/SIGNIFICANCE: Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.