Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers.

OPINION STATEMENT: Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes

Assessment of physicochemical parameters in groundwater quality of desert area (Tharparkar) of Pakistan

In Tharparkar desert, the main source of water supply is groundwater. Water for domestic use is normally collected from open dug wells. For this study, twenty-five groundwater samples were collected from the open dug well of Talukas of Tharparkar, Southern Sindh, Pakistan, to evaluate its quality and suitability for drinking, domestic, and agricultural use. The findings in this paper are based on an examination of regional variations and the use of a geographic information system (GIS), which incorporates the results of 25 well water samples collected from six villages in Taluka Mithi Tharparkar. The study's findings reveal excessive concentrations of physical and chemical characteristics in the majority of locations, in contradiction to the World Health Organization's (WHO) recommendations for drinking water. Majority of wells in the studied area the TDS were ranging from 800 to 11,000 mg/l. However, villages of Madhu, Dharar and Mithi were found to have high TDS that exceeded 1000 mg/L, which was a major cause of health problems in the area. Moreover, the total concentration of arsenic and fluoride in water samples varied between 0.0015 and 80 μg/L and 0.1–5.1 mg/l respectively. The inorganic form of As, was found to be 95% of the total As level in the regional drinking water. The concentration of Fluoride in areas of Mithi, Dharar, Harmar and Satar was found above the permissible limits. Furthermore, results indicate that correlations among water parameters dropped, and examined values were inconsequential. Statistical analysis (a linear regression method) was performed, for predicting the concentrations of groundwater quality parameters. A significant positive association between 1% and 4% was found between different parameters. The collected health data indicate that the study area has waterborne diseases. Therefore, comprehensive groundwater monitoring and management are required in the studied area to protect populations from various diseases caused by poor water quality

In the NadR Regulon, Adhesins and Diverse Meningococcal Functions Are Regulated in Response to Signals in Human Saliva

The Neisseria meningitidis regulator NadR was shown to repress expression of the NadA adhesin and play a major role in NadA phase-variable expression. In this study, we identified through microarray analysis over 30 genes coregulated with nadA in the NadR mutant and defined members of the NadR regulon through in vitro DNA-binding assays. Two distinct types of promoter architectures (I and II) were identified for NadR targets, differing in both the number and position of NadR-binding sites. All NadR-regulated genes investigated were found to respond to 4-hydroxyphenylacetic acid (4HPA), a small molecule secreted in human saliva, which was previously demonstrated to induce nadA expression by alleviating NadR-dependent repression. Interestingly, two types of NadR 4HPA responsive activities were found on different NadR targets corresponding to the two types of genes identified by different promoter architectures: while NadA and the majority of NadR targets (type I) are induced, only the MafA adhesins (type II) are corepressed in response to the same 4HPA signal. This alternate behavior of NadR was confirmed in a panel of strains in response to 4HPA and after incubation in saliva. The in vitro NadR binding activity at type I and type II promoter regions is differentially affected by 4HPA, suggesting that the nature of the NadR binding sites may define the regulation to which they will be subjected. We conclude that NadR coordinates a broad transcriptional response to signals present in human saliva, mimicked in vitro by 4HPA, enabling the meningococcus to adapt to the relevant host niche