To SHARE or not to SHARE: Exploring incarcerated women's decisions about enrolling in exposure-based group therapy.

Exposure therapies effectively treat traumatic stress sequelae, including that which follows sexual violence victimization (SVV). Carceral facilities house women with significantly higher rates of SVV than community samples, yet they rarely implement this form of treatment. In this study, women with histories of SVV (n = 63) completed semistructured qualitative interviews about their decision to enroll or not enroll in an exposure-based group therapy called Survivors Healing from Abuse: Recovery through Exposure while incarcerated. All study participants were previously incarcerated in a prison, where they were offered the opportunity to enroll in Survivors Healing from Abuse: Recovery through Exposure. We used the theory of planned behavior to analyze factors that affected enrollment decisions. Results revealed that enrollment decisions among incarcerated women can be categorized within the theory of planned behavior framework. Interview responses indicated that recognizing current problems as related to experiences of SVV, holding positive attitudes about mental health treatment, observing peers engaging in help-seeking behaviors, and perceiving treatment as accessible were linked with enrollment. Negative perceptions of treatment, fear of judgment, and negative peer influence (e.g., distrust of peers) were linked to decisions not to enroll. While certain beliefs were influenced by contextual features of incarceration (e.g., peer interactions outside of group therapy), many overlapped with factors found to influence help-seeking among nonincarcerated populations. Findings have implications for how to engage members of underserved populations in resource-deprived contexts who have a great need for treatment of traumatic symptoms secondary to sexual violence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Quantitative target engagement of RIPK1 in human whole blood via the cellular thermal shift assay for potential pre-clinical and clinical applications.

The cellular thermal shift assay (CETSA®) is a target engagement method widely used for preclinical characterization of small molecule compounds. CETSA® has been used for semi-quantitative readouts in whole blood with PBMC isolation, and quantitative, plate-based readouts using cell lines. However, there has been no quantitative evaluation of CETSA® in unprocessed human whole blood, which is preferred for clinical applications. Here we report two separate assay formats - Alpha CETSA® and MSD CETSA® - that require less than 100 µL of whole blood per sample without PBMC isolation. We chose RIPK1 as a proof-of-concept target and, by measuring engagement of seven different inhibitors, demonstrate high assay sensitivity and robustness. These quantitative CETSA® platforms enable possible applications in preclinical pharmacokinetic-pharmacodynamic studies, and direct target engagement with small molecules in clinical trials.

Does Group Size Matter? Group Size and Symptom Reduction Among Incarcerated Women Receiving Psychotherapy Following Sexual Violence Victimization.

Survivors Healing from Abuse: Recovery through Exposure (SHARE) is an eight-week therapy group for incarcerated women who have experienced sexual violence victimization. SHARE requires each member to complete an imaginal exposure and to listen when others share their experiences of victimization. While trauma-focused group interventions including SHARE are associated with reductions in internalizing symptoms, little work has examined how group characteristics predict symptom decreases. The purpose of this study was to examine whether group size was associated with symptom changes pre- to post-treatment. Participants (n=140 across 29 groups) completed self-report measures of posttraumatic stress symptoms before and after completing SHARE. Multilevel modeling revealed the majority of the variance in post-treatment symptoms was attributed to individual factors rather than group factors. Symptom change was comparable for groups of two to eight women; declines in symptom improvement were observed at a group size of ten participants.

Epidemiology and clinical manifestations of different enterovirus and rhinovirus types show that EV-D68 may still have an impact on severity of respiratory infections.

Respiratory infections are often caused by enteroviruses (EVs). The aim of this study was to identify whether certain types of EV were more likely to cause severe illness in 2016, when an increasing spread of upper respiratory infections was observed in Gothenburg, Sweden. The EV strain in 137 of 1341 nasopharyngeal samples reactive for EV by polymerase chain reaction could be typed by sequencing the viral 5'-untranslated region and VP1 regions. Phylogenetic trees were constructed. Patient records were reviewed. Hospital care was needed for 46 of 74 patients with available medical records. The majority of the patients (83) were infected with the rhinovirus (RV). The remaining 54 were infected with EV A, B, C, and D strains of 13 different types, with EV-D68 and CV-A10 being the most common (17 vs. 14). Significantly more patients with EV-D68 presented with dyspnea, both when compared with other EV types (p = 0.003) and compared to all other EV and RV infections (p = 0.04). Phylogenetic analysis of the sequences revealed the spread of both Asian and European CV-A10 strains and 12 different RV C types. This study showed an abundance of different EV types spreading during a year with increased upper respiratory increased infections. EV-D68 infections were associated with more severe disease manifestation. Other EV and RV types were more evenly distributed between hospitalized and nonhospitalized patients. The EV type CV-A10 was also found in infected patients, which warrants further studies and surveillance, as this pathogen could cause more severe disease and outbreaks of hand, foot, and mouth disease.

Decreases in psychiatric symptoms persist following exposure-based group therapy for sexual violence victimization among incarcerated women.

Survivors Healing from Abuse: Recovery through Exposure (SHARE) is a brief, exposure-based group treatment for incarcerated female survivors of sexual violence. Preliminary evaluations of SHARE showed declines in depression and posttraumatic stress disorder (PTSD) symptoms from pre- to posttreatment. However, prior investigations have not included a longitudinal follow-up period and thus knowledge of whether therapeutic benefits persist following the termination of the group is lacking. Here, we examined data from 57 incarcerated women who completed SHARE and provided follow-up data while still incarcerated (M = 95 days posttreatment). Results from a one-way repeated-measures ANOVA showed significant reductions in PTSD and depression symptoms from pre- to posttreatment (large effect sizes), with symptoms further reduced during the follow-up period. In addition, McNemar tests showed a significant reduction in the proportion of participants at or above the clinical cut-off for probable PTSD and depression from pre- to posttreatment as well as from posttreatment to the follow-up assessment. Together, results suggest that the therapeutic benefits of SHARE persist after treatment is completed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

"I'm not alone, my story matters": Incarcerated women's perspectives on the impact and acceptability of group psychotherapy involving imaginal exposure to sexual assault memories.

BACKGROUND: Although it is clear that incarcerated women need access to effective therapies for trauma sequelae, some have argued that one of the most effective treatments - exposure therapy - should not be provided in carceral settings due to the presumed lack of safety and stability making such an intervention inappropriate. Group therapy, the typical mode of intervention in prisons, has also been presumed to be unacceptable for exposure-based processing due to assumptions that hearing others' trauma narratives would be traumatizing and unhelpful to listeners. However, there is a lack of data to support either of the aforementioned assumptions. This study examined the acceptability of an exposure-based group therapy for women survivors of sexual violence who were currently incarcerated (N = 61) by asking women themselves about their experiences completing an exposure-based group therapy protocol (SHARE; Survivors Healing from Abuse: Recovery through Exposure) while incarcerated. We assessed women's reasons for enrolling in the group, satisfaction with various therapy components (e.g., exposure, skill-building) and the treatment overall, and experiences of both sharing and listening to trauma narratives using a feedback survey that included a mix of multiple-choice and open-ended questions. Treatment dropout was examined as an additional index of acceptability. RESULTS: Treatment completion was very high (88.8%). Nearly all women who completed the group reported that they would recommend it to other incarcerated women (96.7%, with the remaining 3.3% reporting "it depends"). Qualitative results revealed overwhelmingly positive feedback about the effect of the group and indicated that sharing and listening to trauma narratives in a group setting serve discrete but dually important functions. Specifically, women almost universally experienced listening to others' trauma narratives (i.e., exposures) in the SHARE group context as helpful-making them feel less alone and normalizing their experiences. Sharing one's own story primarily provided an emotional release and/or transformation (i.e., an intrapersonal rather than interpersonal function). CONCLUSIONS: Our findings challenge common concerns about the appropriateness of 1) prison as a context for trauma-focused treatments, including exposure and 2) sharing trauma narratives in a group setting. Unless empirical evidence demonstrating harm is uncovered, best practices for PTSD and other trauma-related sequelae-those recommended in reputable treatment guidelines and interventions like SHARE that incorporate components shown to be effective (e.g., cognitive challenging, exposure)-should be offered to incarcerated women as part of standard of care.

Interpersonal vs. Non-Interpersonal Cumulative Traumas and Psychiatric Symptoms in Treatment-Seeking Incarcerated Women.

Incarcerated women are at elevated risk of lifetime trauma exposure. Prevalence rates of trauma exposure and how these events relate to specific domains of psychiatric symptomology among this group are lacking. This study hypothesized a greater range of diverse cumulative trauma experiences (CTEs) would be positively associated with psychiatric symptoms in general (depression, PTSD, distress tolerance), but that interpersonal CTEs in particular would be uniquely associated with greater symptoms of guilt and shame. A total of 112 women (87% White, Mage = 34 years) seeking treatment for a history of sexual violence victimization participated in the study. Women incarcerated for nonviolent offenses at two minimum-security prisons completed self-report measures of exposure to diverse traumatic events and internalizing symptoms. On average, participants reported a history of experiencing 5.46 traumatic event types. Total CTEs was significantly associated with all psychiatric variables in the expected direction. While both interpersonal and non-interpersonal CTEs were positively associated with levels of PTSD, depression, and distress intolerance, only interpersonal CTEs were significantly associated with guilt and shame. Traumatic experiences that are interpersonal in nature may confer specific risk for psychiatric symptoms in victims.

Implementing and Sustaining SHARE: An Exposure-Based Psychotherapy Group for Incarcerated Women Survivors of Sexual Violence.

Although incarcerated women are a highly victimized population, therapy for sexual violence victimization (SVV) sequela is not routinely offered in prison. SHARE is a group therapy for SVV survivors that was successfully implemented and sustained in a women's correction center. Here, we aimed to identify implementation factors and strategies that led to SHARE's success and describe incarcerated women's perspectives on the program. We conducted a retrospective process evaluation using interviews structured according to EPIS, a well-established implementation science framework. Participants (N = 22) were incarcerated women, members of the SHARE treatment team, and members of the correction center's leadership, therapeutic team, and volunteer program. Factors that facilitated SHARE implementation varied by EPIS phase and organization. Positive inter-organizational and interpersonal relationships were key across phases, as were the synergies between both the strengths and needs of each organization involved in implementation. Incarcerated women reported a strong need for SHARE and did not report any concerns about receiving trauma therapy in a carceral setting. Therapy for SVV sequelae, including exposure-based therapy, is possible to implement and sustain in carceral settings. Community-academic partnerships may be a particularly feasible way to expand access to SVV therapy for incarcerated women.

TOB-STOP-COP (TOBacco STOP in COPd trial): study protocol-a randomized open-label, superiority, multicenter, two-arm intervention study of the effect of "high-intensity" vs. "low-intensity" smoking cessation intervention in active smokers with chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15-20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. METHODS: This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, "low intensity" group) or an intervention ("high-intensity" group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and "buddy-matching" (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. DISCUSSION: The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019.

Heterogeneity of Human Pancreatic Islet Isolation Around Europe: Results of a Survey Study.

BACKGROUND: Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries. METHODS: A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan. RESULTS: Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations per year over the last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions per year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation, and release criteria for transplantation (glucose-stimulated insulin secretion tests, islet numbers, and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities. CONCLUSIONS: The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria.

Replicating outcomes of Survivors Healing from Abuse: Recovery through Exposure (SHARE): A brief exposure-based group treatment for incarcerated survivors of sexual violence.

OBJECTIVE: Survivors Healing from Abuse: Recovery through Exposure (SHARE) is a group treatment for incarcerated women that targets sexual abuse sequelae. Previous research on SHARE found significant reductions in posttraumatic stress disorder (PTSD), depression, and generalized anxiety disorder (GAD) symptoms among completers. However, evidence for SHARE has been limited to open pilot studies conducted in one prison. Therefore, this study sought to replicate the results of previous SHARE studies in a separate facility. METHOD: Thirty-two women incarcerated in a minimum-security prison participated in an open trial of SHARE. Six separate groups were conducted, each consisting of eight 1.5-hr sessions. RESULTS: Pre- to posttreatment symptom reductions in PTSD, depression, and GAD were statistically significant with large effect sizes. Moreover, 21-37% of treatment completers evidenced reliable change in their symptom reduction during the course of treatment. Most women who did not evidence reliable change were already below the clinical cutoff on the corresponding symptom measure at pre-treatment and remained below by post-treatment. CONCLUSIONS: These results are consistent with prior studies of SHARE and provide additional support for the positive outcomes of this brief, targeted trauma-focused treatment for incarcerated women. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Sexual Victimization and Mental Illness Prevalence Rates Among Incarcerated Women: A Literature Review.

Incarcerated women evidence high rates of both interpersonal trauma and mental illness. In particular, the rates of sexual violence victimization are so high that some researchers have suggested that sexual abuse may be a pathway to prison for women, likely through the development of mental illness, including substance abuse. This review article summarizes the literature on sexual victimization (n = 32 articles; 28 independent studies) and mental illness (n = 11 articles; 8 independent studies) prevalence among samples of incarcerated women (Ns ≥ 100) in context of methodological choices within included articles. Best estimates for sexual victimization from studies using established survey methods were as follows: 50-66% for child sexual abuse, 28-68% for adult sexual abuse, and 56-82% for lifetime sexual assault. Although data directly comparing prevalence of sexual victimization among incarcerated women to prevalence for other groups are limited, the existing data indicate that incarcerated women have significantly greater exposure than incarcerated men and community samples of women. Moreover, compared to findings from the National Comorbidity Survey-Replication, incarcerated women evidence greater prevalence of most lifetime and current mental illnesses, especially depressive disorders, post-traumatic stress disorder, and substance use disorders. Surprisingly, only two independent studies have investigated the overlap between sexual victimization and mental illness in samples of incarcerated women. Both studies found disproportionally high rates of mental illness among victims of sexual violence. Suggestions and implications for research, policy, and practice are discussed.

Hepatitis E virus genotype 3 is associated with gallstone-related disease.

Objective: Hepatitis E virus (HEV) genotype 3 is endemic in Northern Europe and despite a high seroprevalence of anti-HEV IgG antibodies among blood donors (≈17%), few clinical cases are notified in Sweden. Low awareness of hepatitis E and its possible symptoms may contribute to this discrepancy. The aim of this study was to investigate the prevalence of acute HEV infection among hospital admitted patients with abdominal pain and elevated liver enzymes.Materials and methods: During 2016-2017, 148 adult patients with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice normal levels were prospectively enrolled at surgical wards at three Swedish hospitals. Serum samples were analyzed for HEV RNA as well as anti-HEV IgM and IgG, and medical records were reviewed.Results: Six (6/148, 4.1%) patients were HEV infected confirmed by detectable HEV RNA, but only one of these patients had detectable anti-HEV antibodies. Four of the HEV infected patients were diagnosed with gallstone-related disease: three with biliary pancreatitis and one with biliary colic. The remaining two were diagnosed with bowel obstruction and pancreatic malignancy. Four HEV strains were typed by sequencing to genotype 3.Conclusions: This study identified acute HEV3 infection in 4% of the patients with elevated liver enzymes admitted to a surgical ward. HEV infection was not the solitary disease leading to hospitalization, instead it was found to be associated with other surgical conditions such as gallstone-related disease including biliary pancreatitis. Additionally, HEV RNA might be the preferential diagnostic tool for detecting ongoing HEV infection.

Comparing the Effects of the mTOR Inhibitors Azithromycin and Rapamycin on In Vitro Expanded Regulatory T Cells.

Adoptive transfer of autologous polyclonal regulatory T cells (Tregs) is a promising option for reducing graft rejection in allogeneic transplantation. To gain therapeutic levels of Tregs there is a need to expand obtained cells ex vivo, usually in the presence of the mTOR inhibitor Rapamycin due to its ability to suppress proliferation of non-Treg T cells, thus promoting a purer Treg yield. Azithromycin is a bacteriostatic macrolide with mTOR inhibitory activity that has been shown to exert immunomodulatory effects on several types of immune cells. In this study we investigated the effects of Azithromycin, compared with Rapamycin, on Treg phenotype, growth, and function when expanding bulk, naïve, and memory Tregs. Furthermore, the intracellular concentration of Rapamycin in CD4+ T cells as well as in the culture medium was measured for up to 48 h after supplemented. Treg phenotype was assessed by flow cytometry and Treg function was measured as inhibition of responder T-cell expansion in a suppression assay. The concentration of Rapamycin was quantified with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Azithromycin and Rapamycin both promoted a FoxP3-positive Treg phenotype in bulk Tregs, while Rapamycin also increased FoxP3 and FoxP3+Helios positivity in naïve and memory Tregs. Furthermore, Rapamycin inhibited the expansion of naïve Tregs, but also increased their suppressive effect. Rapamycin was quickly degraded in 37°C medium, yet was retained intracellularly. While both compounds may benefit expansion of FoxP3+ Tregs in vitro, further studies elucidating the effects of Azithromycin treatment on Tregs are needed to determine its potential use.

Widespread pain and pain intensity in patients with early rheumatoid arthritis. A cross-sectional comparison between smokers and non-smokers.

AIM: The aim was to investigate if smoking status at time for diagnoses of rheumatoid arthritis was associated with pain intensity or pain spread. DESIGN: A cross-sectional study conducted in 2012-2013. METHODS: Seventy-eight patients, of whom 16 were current smokers and 62 never or previous smokers, with newly diagnosed rheumatoid arthritis were assessed as to pain intensity, widespread pain and disease activity. RESULTS: Of the participants, 56% had unacceptable pain, 77% had spread pain and 28% had chronic widespread pain. There were no differences in pain intensity, widespread pain or chronic widespread pain between smoking status groups. However, there was a positive association between pain intensity and disease activity, r = 0.52. CONCLUSION: In this study, patients with early rheumatoid arthritis had a high-frequency unacceptable pain and wide spread pain, irrespective of smoking status. However, we cannot exclude that the inflammatory-associated pain overshadowed a possible negative effect of smoking.

Islets for Research: Nothing Is Perfect, but We Can Do Better.

In December 2018, Diabetes and Diabetologia began requiring authors of papers reporting data obtained from studies on human islets to report critical characteristics of the human islets used for research. The islet community was asked to provide feedback on it. Here is the contribution by the European Consortium for Islet Transplantation.

Hepatitis E virus strains infecting Swedish domestic pigs are unique for each pig farm and remain in the farm for at least 2 years.

Hepatitis E virus (HEV) genotype 3 (HEV3) is distributed globally and infects both humans and animals, mainly domestic pigs and wild boars, which are the major reservoirs. In this study, the prevalence of HEV among Swedish pigs was investigated by HEV RNA analysis in 363 faecal samples from 3-month-old piglets sampled twice (2013 and 2014) in 30 Swedish pig farms. Four different types of farms were investigated; organic, conventional closed (keeping the sow), satellites in a sow pool (conventional farms sharing sows) and conventional non-closed farms (purchasing gilts). More than two-thirds (77%) of the farms had HEV-infected pigs. HEV RNA was found in faeces from 79 pigs (22%). Partial ORF1 could be sequenced in 46 strains. Phylogenetic analysis revealed a unique HEV3 strain for each farm. Strains sampled more than a year apart from the same farm were closely related, indicating that the same HEV strain is present for several years on the farm. Despite that only 4% of the Swedish pig farms were investigated, two farms had strains similar to those from humans, another had strains similar to wild boar HEV. The uniqueness of strains from each farm indicates a possibility to identify a source of infection down to farm level. This knowledge may be used by the farms to investigate the effectiveness of good hygiene routines to reduce the amount of HEV and thus the infection risk in the farm, and for Swedish public health authorities to identify cases of HEV transmissions from consumption of uncooked pork.

Genetically similar hepatitis E virus strains infect both humans and wild boars in the Barcelona area, Spain, and Sweden.

Hepatitis E virus (HEV) is a hepatotropic virus, endemic in Europe where it infects humans and animals, with domestic pigs and wild boars as main reservoirs. The number of HEV-infected cases with unknown source of infection increases in Europe. There are human HEV strains genetically similar to viruses from domestic pigs, and zoonotic transmission via consumption of uncooked pork meat has been shown. Due to continuous growth of the wild boar populations in Europe, another route may be through direct or indirect contacts with wild boars. In the Collserola Natural Park near Barcelona, Spain, the wild boars have spread into Barcelona city. In Sweden, they are entering into farmlands and villages. To investigate the prevalence of HEV and the risk for zoonotic transmissions, the presence of antibodies against HEV and HEV RNA were analysed in serum and faecal samples from 398 wild boars, 264 from Spain and 134 from Sweden and in sera from 48 Swedish patients with HEV infection without known source of infection. Anti-HEV was more commonly found in Spanish wild boars (59% vs. 8%; p < 0.0001) while HEV RNA had similar prevalence (20% in Spanish vs. 15% in Swedish wild boars). Seven Swedish and three Spanish wild boars were infected with subtype 3f, and nine Spanish with subtype 3c/i. There were three clades in the phylogenetic tree formed by strains from wild boars and domestic pigs; another four clades were formed by strains from humans and wild boars. One strain from a Spanish wild boar was similar to strains from chronically infected humans. The high prevalence of HEV infections among wild boars and the similarity between wild boar HEV strains and those from humans and domestic pigs indicate that zoonotic transmission from wild boar may be more common than previously anticipated, which may develop into public health concern.

Protein Kinase R Is Constitutively Expressed in the Human Pancreas.

Viral infection of the insulin-producing cells in the pancreas has been proposed in the etiology of type 1 diabetes. Protein kinase R (PKR) is a cytoplasmic protein activated through phosphorylation in response to cellular stress and particularly viral infection. As PKR expression in pancreatic beta-cells has been interpreted as a viral footprint, this cross-sectional study aimed at characterizing the PKR expression in non-diabetic human pancreases. PKR expression was evaluated in pancreas tissue from 16 non-diabetic organ donors, using immunohistochemistry, qPCR, and western blot. Immunohistochemistry and western blot showed readily detectable PKR expression in the pancreatic parenchyma. The qPCR detected PKR mRNA in both endocrine and exocrine samples, with a slightly higher expression in the islets. In conclusion, PKR is constitutively expressed in both endocrine and exocrine parts of the pancreas and its expression should not be interpreted as a viral footprint in pancreatic beta cells.

BCG-induced cytokine release in bladder cancer cells is regulated by Ca2+ signaling.

Bacillus Calmette-Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca2+ (calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca2+ response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca2+ signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.