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The treatment options for prostate cancer typically entail active surveillance, surgery, radiation, or a combination of the above. Disease recurrence remains a concern, with a wide range of recurrence rates having been reported in the literature. In the setting of recurrence, the salvage treatment options include salvage prostatectomy, salvage high-intensity focused ultrasound (HIFU), stereotactic body radiotherapy (SBRT), salvage brachytherapy, and salvage cryoablation. In this review, we analyze the currently available data related to salvage cryoablation for recurrent prostate cancer following radiation.

When interacting with infants, humans often alter their speech and song in ways thought to support communication. Theories of human child-rearing, informed by data on vocal signalling across species, predict that such alterations should appear globally. Here, we show acoustic differences between infant-directed and adult-directed vocalizations across cultures. We collected 1,615 recordings of infant- and adult-directed speech and song produced by 410 people in 21 urban, rural and small-scale societies. Infant-directedness was reliably classified from acoustic features only, with acoustic profiles of infant-directedness differing across language and music but in consistent fashions. We then studied listener sensitivity to these acoustic features. We played the recordings to 51,065 people from 187 countries, recruited via an English-language website, who guessed whether each vocalization was infant-directed. Their intuitions were more accurate than chance, predictable in part by common sets of acoustic features and robust to the effects of linguistic relatedness between vocalizer and listener. These findings inform hypotheses of the psychological functions and evolution of human communication., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: To identify prognostic factors for overall survival (OS) in patients with malignant ureteral obstruction (MUO) from gynecologic malignancy (GM), with the goal of improving patient selection for urinary diversion., Materials and Methods: Retrospective review of 126 patients with MUO from GM at two academic centers from 2011-2019. Factors related to OS identified by Cox regression proportional hazard model. In patients with incomplete survival data (n = 30), hospice was used as a surrogate for death. Multivariate models and receivers operating characteristics (ROC) curves were created for hemoglobin and albumin values., Results: Overall median survival was 6.2 months. On univariate analysis, age at diagnosis, Charlson Comorbidity Index (CCI) ≥ 8, advanced clinical stage, ascites, pleural effusion, albumin, and hemoglobin were associated with poor OS. OS was higher for those receiving ureteral stenting as compared with no intervention. There was no survival difference based on hydronephrosis grade, stent failure (SF), or creatinine at the time of intervention. On multivariate analysis, albumin < 2.85 g/dL and hemoglobin < 9.6 g/dL were predictive of poor OS., Conclusions: OS in patients with MUO due to GM is poor. Several prognostic factors for poor survival including low serum albumin and hemoglobin were identified. Ureteral stenting was associated with improved OS compared to observation, but selection bias likely contributed to this result. Additional studies are needed to clarify this finding. These data can be utilized to counsel patients regarding outcomes after urinary diversion in the setting of MUO and perhaps avoid additional procedures in some of these patients who will not derive meaningful benefit.

Introduction: Lower extremity lymphedema is a major source of morbidity in up to 70% of penile cancer patients. Lymphedema is often thought to be incurable, though surgical treatments have started to emerge. This study is the first to apply lymphovenous bypass specifically to penile cancer patients status post lymphadenectomy., Methods: We performed microsurgical lymphovenous bypass in 3 patients who underwent inguinal lymphadenectomy for advanced penile cancer, and later lymph node transplant in 1 patient., Results: The lymphovenous bypass was performed by a trained microsurgeon: Two patients were treated as outpatients for lymphedema, and 1 patient underwent prophylactic lymphovenous bypass simultaneously with initial lymphadenectomy. We saw significant improvement in patient's clinical lymphedema as well as lymphatic drainage on infared imaging for 2 of 3 patients at 12 months, however 1 of these patients did require later lymph node transfer at 24 months., Conclusion: This early proof of concept study shows that these procedures should be considered and studied further in the treatment and prevention of debilitating lymphedema in the penile cancer population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has been shown to improve continence. However, questions remain regarding feasibility and generalizability of technique and outcomes., Objective: To compare the outcomes of 140 consecutive standard robot-assisted radical prostatectomy (S-RARP) versus RS-RARP., Design, Setting, and Participants: A total of 70 S-RARPs were performed followed by 70 RS-RARPs. Demographic, pathologic, and functional outcomes were compared preoperatively and through 12 mo. Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) was used to compare functional outcomes. Logistic and linear regression analyses were utilized to analyze variables associated with EPIC-CP urinary incontinence and overall quality of life (QOL) scores, and oncologic outcomes. Cox regression analysis was used to analyze incontinence at 12 mo., Surgical Procedure: RS-RARP versus S-RARP., Measurements: Patient and tumor characteristics (age, body mass index, prostate-specific antigen, Charlson Comorbidity Index, Gleason group, clinical stage, and Prostate Imaging Reporting and Data System score), perioperative outcomes (console time, estimated blood loss, postoperative complications, and length of stay), oncologic outcomes (positive surgical margin [PSM], and biochemical recurrence), overall and 12-mo continence rates (zero pads and zero to one safety pad), time to continence, potency (erection sufficient for sexual activity), EPIC-CP urinary incontinence, sexual function, and overall QOL scores., Results and Limitations: Median follow-up for S-RARP versus RS-RARP was 46.3 versus 12.3 mo. RS-RARP versus S-RARP had improved overall continence rates at total follow-up (95.7% vs 85.7%, p = 0.042) and 12-mo follow-up (97.6% vs 81.4%, p = 0.002), and faster return to continence (zero to one safety pad, 44 vs 131 d, p < 0.001). RS-RARP EPIC-CP urinary incontinence and overall QOL scores remained significantly better at 12 mo. There were no differences in overall PSM rates, although RS-RARP had lower rates of nonfocal PSMs. There were no differences in sexual function. In multivariate analysis, RS-RARP was significantly associated with improved 12-mo EPIC-CP urinary incontinence and improved QOL scores, but was not associated with PSM or biochemical recurrence. Limitations include retrospective study design and unequal follow-up; however, significantly better RS-RARP continence at 12 mo is striking despite fewer patients attaining 12-mo follow-up., Conclusions: RS-RARP significantly improves early and long-term continence without compromising oncologic outcomes and leads to overall improved QOL., Patient Summary: Retzius-sparing robot-assisted radical prostatectomy is an emerging technique for robotic radical prostatectomy that improves urinary function and quality of life without compromising cancer control., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the characteristics of women presenting with genitourinary fistula over a 5-year period in Kigali, Rwanda. Genitourinary (GU) fistula is a devastating condition that can result from difficult vaginal deliveries or as a surgical complication. Rwanda has seen notable increases in cesarean section rates as a result of a successful universal health care system. It is unclear how the increase in cesarean section rates may influence the types of fistula diagnosed., Materials and Methods: A cross-sectional study was conducted of women presenting for evaluation to the International Organization for Women and Development in Kigali, Rwanda, between February 1, 2013 and October 31, 2017. Data were collected from medical records, including demographics, surgical history, physical exam findings, and surgical intervention., Results: Two thousand ninety-one women presented for evaluation during the study period, of these 630 (30%) were diagnosed with GU fistula. Of the fistula diagnosed, 392 (62%) were vesicovaginal fistula, 185 (29%) were vesicouterine or vesicocervical, and 56 (9%) were ureterovaginal fistula. The percent of GU fistula that involved the ureter, uterus, and/or cervix significantly increased over the time period: 29.6% in 2013, 34.6% in 2014; 43.0% in 2015, 42.9% in 2016, and 45.3% in 2017., Conclusion: There was a significant increase in the proportion of vesicouterine, vesicocervical, and ureterovaginal fistula presenting in Rwanda over the 5-year period, with the majority occurring after cesarean section., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the effect of surgical experience on peri-operative, functional and oncological outcomes during the first 50 Retzius-sparing robot-assisted radical prostatectomy (RsRARP) cases performed by surgeons naïve to this novel approach., Materials and Methods: We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centres. Pre-, peri- and postoperative features of the first 50 patients operated by each surgeon in all the participating centres were collected. The effect of surgical experience on peri-operative, functional and oncological outcomes was firstly evaluated after stratification by level of surgical experience (initial [≤25 cases] and expert [>25 cases]) and after using locally weighted scatterplot smoothing to graphically explore the relationship between surgical experience and the outcomes of interest., Results: We evaluated 626 patients. The median follow-up was 13 months in the initial group and 9 months in the expert group (P = 0.002). Preoperative features overlapped between the two groups. Shorter console time (140 vs 120 min; P = 0.001) and a trend towards lower complications rates (13 vs 5.5%; P = 0.038) were observed in the expert group. The relationship between surgical experience and console time, immediate urinary continence recovery and Clavien-Dindo grade ≥2 complications was linear, without reaching a plateau, after 50 cases. Conversely, a non-linear relationship was observed between surgical experience and positive surgical margins (PSMs)., Conclusions: In this first report of a multicentre experience of RsRARP during the learning curve, we found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSM rates did not clearly improve over the first 50 cases., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Background: Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) has improved urinary function compared with standard robotic-assisted radical prostatectomy (S-RARP). As RS-RARP spares the dorsal vascular complex, pelvic fascia, and anterior abdominal fascia, it may also lower the incidence of "neglected" postprostatectomy sequelae such as penile shortening, Peyronie's disease, and inguinal hernias., Objective: To determine whether there are patient-perceived differences in penile shortening, Peyronie's disease, and inguinal hernia rates among men undergoing RS-RARP versus S-RARP., Design Setting and Participants: Researchers uninvolved in clinical care and blinded to surgical approach surveyed 60 RS-RARP versus 57 S-RARP men with validated patient-reported items to assess penile shortening, Peyronie's disease, and inguinal hernia sequelae following surgery., Intervention: RS-RARP versus S-RARP., Outcome Measurements and Statistical Analysis: Univariate differences between the two cohorts were analyzed using Student t test. Logistic regression was used to analyze variables associated with postoperative penile shortening. Cox proportional hazards models were used to assess the risk of developing Peyronie's disease and inguinal hernia postoperatively., Results and Limitations: RS-RARP was associated with less patient-reported penile shortening (41.7% vs 64.9%, p  = 0.012), Peyronie's disease (0% vs 8.7%, p  = 0.020), and inguinal hernia (0.0% vs 13.0%, p  = 0.004). In adjusted analyses, RS-RARP (odds ratio [OR] 0.24, 95% confidence interval [CI] 0.09-0.63, p  = 0.004) was associated with lower odds of penile shortening, while a higher body mass index was associated with increased odds of penile shortening (OR 1.13, 95% CI 1.01-1.26, p  = 0.037). RS-RARP was not associated with a decreased risk of Peyronie's disease on Cox proportion hazard model; however, these models are limited due to a limited number of events in our cohort. Limitations include retrospective design, patient-reported outcomes, and small cohorts., Conclusions: RS-RARP is associated with less patient-reported penile shortening and may decrease the risk of Peyronie's disease and postoperative inguinal hernia development. These new findings add to research, showing improved urinary continence and quality of life following RS-RARP; however, a prospective study is needed to validate these findings., Patient Summary: Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) is an evolving surgical technique for prostate cancer treatment, which has shown improved postoperative urinary control compared with the standard technique, likely due to preservation of natural pelvic anatomy. Our findings suggest that the preservation of normal pelvic anatomy during RS-RARP may also reduce the risk of postprostatectomy penile shortening, Peyronie's disease, and inguinal hernia., (© 2020 The Author(s).)

Antibiotic resistance frequently evolves through fitness trade-offs in which the genetic alterations that confer resistance to a drug can also cause growth defects in resistant cells. Here, through experimental evolution in a microfluidics-based turbidostat, we demonstrate that antibiotic-resistant cells can be efficiently inhibited by amplifying the fitness costs associated with drug-resistance evolution. Using tavaborole-resistant Escherichia coli as a model, we show that genetic mutations in leucyl-tRNA synthetase (that underlie tavaborole resistance) make resistant cells intolerant to norvaline, a chemical analog of leucine that is mistakenly used by tavaborole-resistant cells for protein synthesis. We then show that tavaborole-sensitive cells quickly outcompete tavaborole-resistant cells in the presence of norvaline due to the amplified cost of the molecular defect of tavaborole resistance. This finding illustrates that understanding molecular mechanisms of drug resistance allows us to effectively amplify even small evolutionary vulnerabilities of resistant cells to potentially enhance or enable adaptive therapies by accelerating posttreatment competition between resistant and susceptible cells., Competing Interests: Competing interest statement: X.F., J.-T.Z., and Y.S. are employees of BGI. J.S. is an employee of Thermo Fisher Scientific. K.L. and H.L. are employees of Erbi Biosystems.

Although ErbB2-targeted therapeutics have significantly improved ErbB2 + breast cancer patient outcomes, therapeutic resistance remains a significant challenge. Therefore, the development of novel ErbB2-targeting strategies is necessary. Importantly, ErbB2 is a sensitive client protein of heat shock protein 90 (HSP90), which regulates client protein folding, maturation, and stabilization. HSP90 inhibition provides an alternative therapeutic strategy for ErbB2-targeted degradation. In particular, ganetespib, a novel HSP90 inhibitor, is a promising agent for ErbB2 + cancers. Nevertheless, the anti-cancer efficacy and clinical application of ganetespib for ErbB2 + breast cancer is largely unknown. In our study, we examined the anti-cancer effects of ganetespib on ErbB2 + BT474 and SKBR3 breast cancer cells, and isogenic paired cancer cell lines with lentivirus-mediated ErbB2 overexpression. Ganetespib potently inhibited cell proliferation, cell cycle progression, survival, and activation/phosphorylation of ErbB2 and key downstream effectors in ErbB2 + breast cancer cells. Moreover, ganetespib decreased the total protein levels of HSP90 client proteins and reduced ErbB2 protein half-life. ErbB2-overexpressing cancer cells were also more sensitive to ganetespib-mediated growth inhibition than parental cells. Ganetespib also strikingly potentiated the inhibitory effects of lapatinib in BT474 and SKBR3 cells. Ultimately, our results support the application of ganetespib-mediated HSP90 inhibition as a promising therapeutic strategy for ErbB2 + breast cancer.

Heat shock protein 90 (HSP90) regulates several important cellular processes via its repertoire of 'client proteins'. These client proteins have been found to play fundamental roles in signal transduction, cell proliferation, cell cycle progression and survival, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. Thus, HSP90 is an emerging target for cancer therapy. To this end, we evaluated ganetespib (STA-9090), a novel and potent HSP90 inhibitor, for its activity in gastric cancer cell lines. Ganetespib significantly inhibited the proliferation of AGS and N87 human gastric cancer cell lines and potently induced G2/M cell cycle arrest and apoptosis. Upregulation of cleaved poly(ADP-ribose) polymerase (c-PARP), c-caspase-3, c-caspase-8 and c-caspase-9 and suppression of gastric cancer‑associated HSP90 client proteins, including ErbB2, Erk, Akt, mTOR, GSK3 and Src, were observed in ganetespib-treated cells. These findings demonstrate that the ganetespib-induced mechanism of cell growth inhibition involves the activation of death receptor and mitochondrial pathways and the inhibition of receptor tyrosine kinase signaling pathways. Our study implicates ganetespib as a potential strategy for gastric cancer treatment, which warrants further preclinical and clinical investigation.

There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation.

Objective: To determine if energy intake on a low-protein diet (0.6 g protein/kg ideal body weight (ibw)/d) with 70% animal protein (Diet A) or 30% animal protein (Diet B) meets energy expenditure derived from measured resting energy expenditure and activity levels., Design: Patients already on a conventional low-protein diet with 70% animal protein kept a 5-day weighed dietary intake, with a 3-day activity diary, and had their resting metabolic rate (RMR) measured. Patients then switched to a diet with 30% animal protein for a minimum of 2 weeks (range, 2 to 16 weeks) and repeated the weighed intake and RMR measurement., Setting: Predialysis hospital outpatients., Patients: Seven patients were recruited, 5 male. Mean age, 56 years (range, 43 to 78 years); mean serum creatinine 300 micromol/L (range, 180 to 560 micromol/L)., Intervention: Indirect calorimetry used to measure RMR., Main Outcome Measure: RMR compared with standard formulae and total energy expenditure compared with dietary intake., Results: Mean RMR was 5.76 MJ/d (1,385 kcal/d) or 84.9 kJ/kg ibw/d (20.3 kcal/kg ibw/d); which was 108% to 113% of that predicted by standard formulae. Total energy expenditure (RMR plus activity) was 8.35 MJ/d (1,996 kcal/d) or 123.3 kJ/kg/d (29.5 kcal/kg ibw/d). Mean energy intake was 116.3 (27.8 kcal/kg ibw/d) on Diet A and 131.2 (31.4 kcal/kg ibw/d) on Diet B (P = .096) with 3 of the 7 patients meeting their energy expenditure on Diet A and 4 on Diet B., Conclusion: RMR of patients with chronic renal failure is within expected range for healthy individuals, and the activity of these relatively fit patients similar to healthy individuals with light to moderate activity. Energy intake on the low-protein diets failed to meet energy expenditure in 4 patients on Diet A and 3 patients on Diet B. Low energy intake may contribute to the development of malnutrition in some patients., (Copyright 2003 by the National Kidney Foundation, Inc.)

An innovative approach of using waste glass in cement production was proposed and tested in a laboratory and cement production plant. The laboratory characterization of 32 types of glass show that the chemical composition of glass does not vary significantly with its color or origin but depends on its application. The alkali content of glass, a major concern for cement production varies from 0 to 22%. For the glass bottles mainly found in Hong Kong waste glasses, the alkali content (Na2O) ranges from 10 to 19% with an average around 15%. There is no significant change of the SO2 content in the gas exhaust of the rotary kiln when about 1.8 t/h of glass bottles were loaded along with the 280-290 t/h raw materials. The content of NOx, mainly depends on the temperature of the kiln, does not show significant change either. The SO3 content of the clinker is comparable with that obtained without the loading of glass. The alkaline content shows a slight increase but still within three times the standard deviation obtained from the statistical data of the past year. The detailed analysis of the quality of the cement product shows that there is not any significant impact of glass for the feeding rate tested.

BACKGROUND: Minority communities are becoming increasingly concerned that the rapid growth of managed care activities will lead to a deterioration of their limited health care services and of the diminution of the primary health care providers. A generally expressed opinion among Asian and Pacific Islander Americans &lpar;APIAs&rpar; is that where there are under&shy;represented physicians groups, especially those who are culturally competent and ethnically sensitive, any health care reform strategy to control cost by cutting program funds is likely to compound the problem of under&shy;representation of the provider community, and would result in greater medically under&shy;serviced areas and populations. In contrast, where there are culturally competent and ethnically sensitive physicians serving their communities, health care is more accessible and of better quality. Physicians and other health care providers working in under&shy;served APIA areas are concerned with the loss of their patients to newly formed health maintenance organizations, the increased hassle of paperwork, the increased levels of patient care activities, and the disincentives and erosion of their financial base. In California, the number of managed care programs leads the nations. Moreover, in seventeen California counties, the Medicaid program is being streamlined under a managed care delivery system. The concern among API communities is the loss of access, availability and acceptability of care. Research and data collection on these issues need to be conducted to assess and evaluate the impact of managed care delivery on the health of these populations. METHODS: Information from literature reviews, data from community health centers, 1990 Census data compiled and analyzed by the Asian and Pacific Islander Center for Census Information and Services &lpar;ACCIS&rpar; program at the Asian and Pacific Islander American Health Forum, and personal communications were the sources of information for this presentation. FINDINGS: The provision of health care services will be more difficult as the managed care movement grows. The supply of physicians providing primary care to the APIA communities is expected to become more acute. The number of primary care physicians is not sufficient to meet the needs of the APIA communities. CONCLUSIONS: The delivery of medical services must be culturally competent and ethnically sensitive. Special interventions are suggested to improve access, acceptability, and appropriateness of health services for the APIA populations. A mentorship program, beginning in the states with the largest numbers of APIAs targeting high school, college, and post-graduate students is suggested as a method to heighten students' sense of social responsibility, and to create the desire and incentive to work in under&shy;served APIA communities.