Mycorrhizal fungus Serendipita indica-associated acid phosphatase rescues the phosphate nutrition with reduced arsenic uptake in the host plant under arsenic stress.

Symbiotic interactions play a vital role in maintaining the phosphate (Pi) nutrient status of host plants and providing resilience during biotic and abiotic stresses. Serendipita indica, a mycorrhiza-like fungus, supports plant growth by transporting Pi to the plant. Despite the competitive behaviour of arsenate (AsV) with Pi, the association with S. indica promotes plant growth under arsenic (As) stress by reducing As bioavailability through adsorption, accumulation, and precipitation within the fungus. However, the capacity of S. indica to enhance Pi accumulation and utilization under As stress remains unexplored. Axenic studies revealed that As supply significantly reduces intracellular ACPase activity in S. indica, while extracellular ACPase remains unaffected. Further investigations using Native PAGE and gene expression studies confirmed that intracellular ACPase (isoform2) is sensitive to As, whereas extracellular ACPase (isoform1) is As-insensitive. Biochemical analysis showed that ACPase (isoform1) has a Km of 0.5977 µM and Vmax of 0.1945 Unit/min. In hydroponically cultured tomato seedlings, simultaneous inoculation of S. indica with As on the 14thday after seed germination led to hyper-colonization, increased root/shoot length, biomass, and induction of ACPase expression and secretion under As stress. Arsenic-treated S. indica colonized groups (13.33 µM As+Si and 26.67 µM As+Si) exhibited 8.28-19.14 and 1.71-3.45-fold activation of ACPase in both rhizospheric media and root samples, respectively, thereby enhancing Pi availability in the surrounding medium under As stress. Moreover, S. indica (13.33 µM As+Si and 26.67 µM As+Si) significantly improved Pi accumulation in roots by 7.26 and 9.46 times and in shoots by 4.36 and 8.85 times compared to the control. Additionally, S. indica induced the expression of SiPT under As stress, further improving Pi mobilization. Notably, fungal colonization also restricted As mobilization from the hydroponic medium to the shoot, with a higher amount of As (191.01 ppm As in the 26.67 µM As+Si group) accumulating in the plant's roots. The study demonstrates the performance of S. indica under As stress in enhancing Pi mobilization while limiting As uptake in the host plant. These findings provide the first evidence of the As-Pi interaction in the AM-like fungus S. indica, indicating reduced As uptake and regulation of PHO genes (ACPase and SiPT genes) to increase Pi acquisition. These data also lay the foundation for the rational use of S. indica in agricultural practices.

Influence of agro-wastes derived biochar and their composite on reducing the mobility of toxic heavy metals and their bioavailability in industrial contaminated soils.

The agro-waste derived valuable products are prime interest for effective management of toxic heavy metals (THMs). The present study investigated the efficacy of biochars (BCs) on immobilization of THMs (Cr, Zn, Pb, Cu, Ni and Cd), bioaccumulation and health risk. Agro-wastes derived BCs including wheat straw biochar (WSB), orange peel biochar (OPB), rice husk biochar (RHB) and their composite biochar (CB) were applied in industrial contaminated soil (ICS) at 1% and 3% amendments rates. All the BCs significantly decreased the bioavailable THMs and significantly (p < 0.001) reduced bioaccumulation at 3% application with highest efficiency for CB followed by OPB, WSB and RHB as compared to control treatment. The bioaccumulation factor (BAF), concentration index (CI) and ecological risk were decreased with all BCs. The hazard quotient (HQ) and hazard index (HI) of all THMs were <1, except Cd, while carcer risk (CR) and total cancer risk index (TCRI) were decreased through all BCs. The overall results depicted that CB at 3% application rate showed higher efficacy to reduce significantly (p < 0.001) the THMs uptake and reduced health risk. Hence, the present study suggests that the composite of BCs prepared from agro-wastes is eco-friendly amendment to reduce THMs in ICS and minimize its subsequent uptake in vegetables.

The present study has a scientific research scope, based on reduction of bioavailability and bioaccumulation of toxic heavy metals (THMs) by the addition of biochars derived from agro-wastes and their composite biochar (CB), thereby decreasing the potential health risk. Limited study has been conducted, especially on the impact of CB in THMs-contaminated soil. This study could fill the scientific research gap and provides useful information for mitigation of THMs present in contaminated soil, which could be followed by the Environmental Protection Agency, Ministry of Agriculture and farmers in degraded lands.

Giant Cell Tumor of the Tendon Sheath of the Hand: Analysis of Factors Impacting Recurrence.

Background Giant cell tumors of the tendon sheath (GCTTS) of the hand are considered the second most common benign tumors of the hand after ganglion cysts. Excision biopsy is considered the standard treatment at present. They are notorious for having a very high rate of recurrence as given in many studies. Many factors are said to be associated with recurrence of the tumors. The goal of this study is to evaluate the long-term results of a series of 48 patients operated on at a single institute and to find out if there is any correlation between the proposed risk factors with recurrence. Methods A retrospective analysis was done in cases of GCTTS operated on between 2015 and 2021. The patients were invited for follow-up for a minimum of 2 years, and the patient files were reviewed. Further data were collected at follow-up including recurrence, range of movement, sensation, skin necrosis, scarring, and digital neuropathy. A data analysis was done. The correlation between the proposed risk factors and recurrence was calculated with the Pearson correlation coefficient. A p -value of less than 0.05 was considered statistically significant. Results During the 6 years, 48 patients were operated on. Recurrence was observed in eight patients (16%) at an average of 38.7 months from the time of surgery. Of the risk factors, tumors with satellite nodules and tumor adjacency to joint correlated significantly with recurrence. No complications were observed during follow-up. Conclusion GCTTS of the hand has a high propensity to recur. The presence of satellite nodules and proximity to interphalangeal joints are two important risk factors for recurrence. Magnification during surgery ensures complete excision of the tumor and reduces the chance of recurrence.

Novel and Innovative Surgical Strategies for Recurrent Rectal Cancer: Uncommon Resections, Local Interventions for Pelvic Reoccurrence, and Intraoperative Radiation Therapy.

The frequency of recurrent rectal cancer has dropped significantly with improved surgical approaches and adjunctive therapies. These recurrences have proven challenging to obtain R0 resection with salvage operations. Meticulous planning, clear understanding of anatomy with imaging, and multispecialty support have become essential in local control and long-term survival with pelvic recurrence of rectal cancer. Technical considerations and prognosis indicators along with role of intraoperative radiation or boost radiation are discussed within.

The role of PPARγ in prostate cancer development and progression.

Advanced and metastatic prostate cancer is often incurable, but its dependency on certain molecular alterations may provide the basis for targeted therapies. A growing body of research has demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) is amplified as prostate cancer progresses. PPARγ has been shown to support prostate cancer growth through its roles in fatty acid synthesis, mitochondrial biogenesis, and co-operating with androgen receptor signalling. Interestingly, splice variants of PPARγ may have differing and contrasting roles. PPARγ itself is a highly druggable target, with agonists having been used for the past two decades in treating diabetes. However, side effects associated with these compounds have currently limited clinical use of these drugs in prostate cancer. Further understanding of PPARγ and novel techniques to target it, may provide therapies for advanced prostate cancer.

MBTPS2 acts as a regulator of lipogenesis and cholesterol synthesis through SREBP signalling in prostate cancer.

BACKGROUND: Prostate cancer is the most common cancer in men in the developed world, with most deaths caused by advanced and metastatic disease which has no curative options. Here, we identified Mbtps2 alteration to be associated with metastatic disease in an unbiased in vivo screen and demonstrated its regulation of fatty acid and cholesterol metabolism. METHODS: The Sleeping Beauty transposon system was used to randomly alter gene expression in the PtenNull murine prostate. MBTPS2 was knocked down by siRNA in LNCaP, DU145 and PC3 cell lines, which were then phenotypically investigated. RNA-Seq was performed on LNCaP cells lacking MBTPS2, and pathways validated by qPCR. Cholesterol metabolism was investigated by Filipin III staining. RESULTS: Mbtps2 was identified in our transposon-mediated in vivo screen to be associated with metastatic prostate cancer. Silencing of MBTPS2 expression in LNCaP, DU145 and PC3 human prostate cancer cells reduced proliferation and colony forming growth in vitro. Knockdown of MBTPS2 expression in LNCaP cells impaired cholesterol synthesis and uptake along with reduced expression of key regulators of fatty acid synthesis, namely FASN and ACACA. CONCLUSION: MBTPS2 is implicated in progressive prostate cancer and may mechanistically involve its effects on fatty acid and cholesterol metabolism.

Antimicrobial peptide moricin induces ROS mediated caspase-dependent apoptosis in human triple-negative breast cancer via suppression of notch pathway.

BACKGROUND: Breast cancer is the world's most prevalent cancer among women. Microorganisms have been the richest source of antibiotics as well as anticancer drugs. Moricin peptides have shown antibacterial properties; however, the anticancer potential and mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored. METHODS: An investigation through in silico analysis, analytical methods (Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), mass spectroscopy (MS), circular dichroism (CD), and in vitro studies, has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. An in-silico analysis was performed to predict the anticancer potential of moricin in cancer cells using Anti CP and ACP servers based on a support vector machine (SVM). Molecular docking was performed to predict the binding interaction between moricin and peptide-related cancer signaling pathway(s) through the HawkDOCK web server. Further, in vitro anticancer activity of moricin was performed against MDA-MB-231 cells. RESULTS: In silico observation revealed that moricin is a potential anticancer peptide, and protein-protein docking showed a strong binding interaction between moricin and signaling proteins. CD showed a predominant helical structure of moricin, and the MS result determined the observed molecular weight of moricin is 4544 Da. An in vitro study showed that moricin exposure to MDA-MB-231 cells caused dose dependent inhibition of cell viability with a high generation of reactive oxygen species (ROS). Molecular study revealed that moricin exposure caused downregulation in the expression of Notch-1, NF-ƙB and Bcl2 proteins while upregulating p53, Bax, caspase 3, and caspase 9, which results in caspase-dependent cell death in MDA-MB-231 cells. CONCLUSIONS: In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in triple negative cancer cells, which could be used in the development of an anticancer drug.

Pharmacological Activities of Rhododendron afghanicum; an Endemic Species of Khyber Pakhtunkhwa, Pakistan.

Majority of different kinds of metabolites having therapeutic characteristics are thought to be stored in medicinal plants. So, the present study was aimed to explore the crude extract of leaves and stem of R. afghanicum for phytochemical screening and various pharmacological activities. Toxicological studies at 100 mg/kg showed 60 % mortality where its safe dose level was 90 mg/kg. Phytochemical screening revealed the presence of alkaloids, glycosides, flavonoids and tannins in both extracts. Bacterial strains were susceptible to (RLEt) and (RLM) crude extracts except Staphylococcus aureus. RSM showed maximum anti-inflammatory activity (20.16 %) followed by RSEt (20.14 %) where lowest activity was displayed by RLEt (18.46 %). Phytotoxic activity showed a substantial dose-dependent phyto-inhibition of Lemna minor. An outstanding cytotoxic potential was displayed with LD50 values of 9.46 and 13.03 µg/ml in both stem extracts. RLEt demonstrated a dose-dependent pain relief at 30, 60 and 90 mg/kg which was 31 %, 40 % and 52 % respectively. A considerable spasmolytic action was observed by the shrinkage of jejunum muscle in albino mice. RLEt at 1000 ppm showed (17 mm) and RLM at 1000 ppm showed (16 mm) zone of inhibition against Aspergillus niger. These findings support and corroborate the traditional applications of R. afghanicum for treating digestive, analgesic and inflammatory ailments.

Continuity of illicit drug use among Malay patients attending methadone clinics in Kelantan, Malaysia.

The study aimed to determine the prevalence of continuity of illicit drug use and its associated factors among Malay opioid users receiving methadone treatment in Kelantan, Malaysia. This cross-sectional study involved a total of 150 respondents. Sociodemographic characteristic of participants, level of religiosity, and quality of life were collected using the self-administered questionnaires. The prevalence of continuity illicit drug use was 38.7% (n = 58) by self-report and 40.7% (n = 61) by positive urine test result for drugs. Positive hepatitis C status and high quality of life in the psychological health domain were associated with low continuity of illicit drug use by self-reported data and urine drug test results. In conclusion, the continuity of illicit drug use among methadone program users is still high, especially among those on methadone therapy for less than 2 years.

CCL25 and CCR9 is a unique pathway that potentiates pannus formation by remodeling RA macrophages into mature osteoclasts.

This study elucidates the mechanism of CCL25 and CCR9 in rheumatoid arthritis (RA). RA synovial fluid (SF) expresses elevated levels of CCL25 compared to OA SF and plasma from RA and normal. CCL25 was released into RA SF by fibroblasts (FLS) and macrophages (MΦs) stimulated with IL-1ß and IL-6. CCR9 is also presented on IL-1ß and IL-6 activated RA FLS and differentiated MΦs. Conversely, in RA PBMCs neither CCL25 nor CCR9 are impacted by 3-month longitudinal TNF inhibitor therapy. CCL25 amplifies RA FLS and monocyte infiltration via p38 and ERK phosphorylation. CCL25-stimulated RA FLS secrete potentiated levels of IL-8 which is disrupted by p38 and ERK inhibitors. CCL25 polarizes RA monocytes into nontraditional M1 MΦs that produce IL-8 and CCL2. Activation of p38 and ERK cascades are also responsible for the CCL25-induced M1 MΦ development. Unexpectedly, CCL25 was unable to polarize RA PBMCs into effector Th1/Th17 cells. Consistently, lymphokine like RANKL was uninvolved in CCL25-induced osteoclastogenesis; however, this manifestation was regulated by osteoclastic factors such as RANK, cathepsin K (CTSK), and TNF-α. In short, we reveal that CCL25/CCR9 manipulates RA FLS and MΦ migration and inflammatory phenotype in addition to osteoclast formation via p38 and ERK activation.

Endofungal Rhizobium species enhance arsenic tolerance in colonized host plant under arsenic stress.

Arsenic (As) is a toxic metalloid that is present in natural surroundings in many forms with severe consequences to sustainable agriculture and human health. Plant growth-promoting Rhizobia have been found involved in the induction of plant tolerance under various biotic and abiotic stresses. An endofungal Rhizobium species associated with arbuscular mycorrhizal fungi (AMF) Serendipita indica deploy beneficial role in the promotion of plant growth and tolerance against various biotic and abiotic stresses. In the current study, we have determined the role of endofungal Rhizobium species in protection of host plant growth under As stress. We observed that endofungal Rhizobium species strain Si001 tolerate AsV up to 25 mM and its inoculation enhances tomato seed germination and seedling growth. A hyper-colonization of Rhizobium species Si001 in tomato roots was observed under As stress and results in modulation of GSH and proline content with reduced ROS. Rhizobium species Si001 colonization in host plant recovered pigment contents (chlorophyll-a and chlorophyll-b up to 189.5% and 192%, respectively), photosynthesis (157%), and water use efficiency (166%) compared to As-treated plants. Interestingly, bacterial colonization results in 40% increased As accumulation in the root, while a reduction in As translocation from root to shoot up to 89% was observed as compared to As treated plants. In conclusion, endofungal Rhizobium species Si001 association with the host plant may improve plant health and tolerance against As stress with reduced As accumulation in the crop produce.

Feasibility and safety of radical prostatectomy for oligo-metastatic prostate cancer: the Testing Radical prostatectomy in men with prostate cancer and oligo-Metastases to the bone (TRoMbone) trial.

OBJECTIVES: To test the feasibility of randomisation to radical prostatectomy (RP) plus pelvic lymphadenectomy in addition to standard-of-care (SOC) systemic therapy in men with newly diagnosed oligo-metastatic prostate cancer. PATIENTS AND METHODS: A prospective, randomised, non-blinded, feasibility clinical trial with an embedded QuinteT Recruitment Intervention (QRI) to optimise recruitment was conducted in nine nationwide tertiary care centres undertaking high-volume robotic surgery. We aimed to randomise 50 men with synchronous oligo-metastatic prostate cancer within an 18-month recruitment period to SOC systemic therapy vs SOC plus RP (intervention arm). The main outcome measures were: ability to randomise patients, optimised by a QRI; EuroQoL five Dimensions five Levels (EQ-5D-5L) questionnaires to capture quality-of-life (QoL) data at baseline and 3 months post-randomisation; routine clinicopathological assessment to capture adverse events and prostate-specific antigen in both arms, plus standard perioperative parameters in the surgical arm. RESULTS: A total of 51 men were randomised within 14 months (one was subsequently deemed ineligible), with 60-83% accrual rate in centres that recruited at least two patients. All patients completed the trial follow-up; one patient in the intervention arm subsequently did not undergo the surgical intervention and one in the SOC arm refused all therapies. The QRI positively impacted recruitment. QoL data showed similarly high functioning in both study arms. Surgery for men with oligo-metastatic prostate cancer was found to be safe and had similar impact on early functional outcomes as surgery for standard indication. CONCLUSION: It is feasible to randomise men with synchronous oligo-metastatic prostate cancer to a surgical intervention in addition to standard systemic therapies. While surgery appeared safe with no substantial impact on QoL in this feasibility study, a large randomised controlled trial is now warranted to examine treatment effectiveness of this additional component in the multimodality management of oligo-metastatic prostate cancer.

The role of restaurant wastewater for producing bioenergy towards a circular bioeconomy: A review on composition, environmental impacts, and sustainable integrated management.

Population inflation has led to the unprecedented increase in urbanization, thus causing negative impacts on environmental sustainability. Recently, there is an upsurge in the number of restaurants due to the changing lifestyles of the people round the globe. For instance, there were 167,490 food and beverage establishments in 2015, representing an annual growth rate of 5.1% since 2010 in Malaysia. The rapid growth of restaurants has implicated a negative impact due to the generation of highly polluted restaurant wastewater (RWW). RWW is mainly generated during the cooking, washing, and cleaning operations. RWW typically contain fat, oil, and grease (FOG) resulting from residues of meat, deep-fried food, baked items and butter, and has caused serious blockages of sewer due to clogging and eventually sewage backup. This has increased the required frequency of cleaning and sanitary sewer overflows (SSOs). Results from the previous studies have shown that FOG can be treated using physical, chemical, and biological processes. Different technologies have been applied for the treatment of FOG and other pollutants (COD, BOD, SS and NH4-N) present in RWW. Therefore, this review aims to provide an in-depth understanding of the characteristics of RWW, chemical and physical characteristics of FOG with the mechanism of its formation and utilization for biocomposites, biogas and biodiesel productions for circular bioeconomy. Besides, this review has discussed the potential treatment technologies comprehensively for RWW which is currently remain understudied. Integrated sustainable management of FOG with technoeconomic analysis of bioproducts, sustainable management with international initiatives and previous studies are also summarized. Hence, this review aims towards providing better alternatives in managing RWW at sources, including its treatment and potential of its biorefinery, therefore eventually contributing towards environmental sustainability.

Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis.

BACKGROUND: Elagolix is effective and safe for treating menorrhagia in women with uterine fibroid. However, it is reported to be associated with hypoestrogenism that can be alleviated by adding estradiol/norethindrone acetate. This systematic review and meta-analysis aimed to determine the effectiveness of elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid by comparing: elagolix versus placebo and elagolix versus estradiol/norethindrone acetate. METHODOLOGY: The Cochrane Central Register of Controlled Trials (CENTRAL 2021, Issue 3 of 12), MEDLINE databases (1980 to December week 1, 2020), and trial registries for relevant randomized clinical trials were used. All randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the dichotomous outcomes and mean differences with 95% confidence intervals. Data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence were assessed. RESULTS: Four randomized controlled trials with 1949 premenopausal women from 323 locations were included. Elagolix improved menstrual blood loss of less than 80 ml (RR 4.81, 95% CI 2.45 to 9.45; four trials, 869 participants; moderate quality evidence) or more than 50% reduction from baseline (RR 4.87, 95% CI 2.55 to 9.31; four trials, 869 participants; moderate quality evidence) compared to placebo. There was no difference in menstrual blood loss of less than 80 ml (RR 1.08, 95% CI 1.00 to 1.16; five trials, 1365 participants; moderate quality evidence) or more than 50% reduction from baseline between the elagolix (RR 1.08, 95% CI 1.01 to 1.15; five trials, 1365 participants; high quality evidence) and elagolix with estradiol/norethindrone acetate. In both comparisons, elagolix has reduced the mean percentage change in uterine and fibroid volume, improved symptoms, and health-related quality of life. More patients had hot flush, and bone mineral density loss in the elagolix treatment compared to both placebo and elagolix with estradiol/norethindrone acetate. CONCLUSIONS: Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women. Review registration PROSPERO CDR 42021233898.

Impact of granulocyte-colony stimulating factor on docetaxel-induced febrile neutropenia in patients with breast cancer.

BACKGROUND: Febrile neutropenia (FN) is a life-threatening complication of Docetaxel-based chemotherapy regimens (DBRs). Prophylactic granulocyte-colony stimulating factor (G-CSF) can reduce the risk of FN. This study investigated the effect of G-CSF on FN in patients receiving DBRs for breast cancer. METHODS: Patients treated between 2015 and 2017 were identified from the hospital's pharmacy database and their medical records were examined retrospectively. Data from patients' first four cycles of DBR were collected. FN rate, FN associated length of hospital stay (FN-LOS), and chemotherapy dose modification/delay due to FN were compared between patients who did (G-CSF group) or did not (non-GCSF group) receive prophylactic G-CSF. RESULTS: Of the 276 included patients, 83.3% received a DBR as adjuvant or neoadjuvant therapy, and 50% received docetaxel as combination therapy. Prophylactic G-CSF was administered with the first cycle of a DBR in 69.9% of patients who were significantly less likely to experience FN compared to the non-G-CSF group (6.2% vs. 15.7%; odds ratio: 0.36 [95% CI: 0.16-0.82]; p = 0.020). Collectively and after the 4 DBR treatment cycles, FN rate (4.8 vs. 8.5; odds ratio: 0.54 [95% CI: 0.30-0.97]; p = 0.043) and the mean FN-LOS (3.55 vs. 5.28 days; t = -2.22; p = 0.037) were reduced in the G-CSF group. There was no difference in DBR dose delay/reduction between both groups in cycles 2-4. CONCLUSION: In patients receiving DBRs for breast cancer, prophylactic G-CSF significantly reduced both the rate of FN and duration of hospitalization for FN.

Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan.

BACKGROUND: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. METHODS: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. RESULTS: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. CONCLUSIONS: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.

Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer: A Randomized Clinical Trial.

Importance: Robot-assisted radical cystectomy is being performed with increasing frequency, but it is unclear whether total intracorporeal surgery improves recovery compared with open radical cystectomy for bladder cancer. Objectives: To compare recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction vs open radical cystectomy. Design, Setting, and Participants: Randomized clinical trial of patients with nonmetastatic bladder cancer recruited at 9 sites in the UK, from March 2017-March 2020. Follow-up was conducted at 90 days, 6 months, and 12 months, with final follow-up on September 23, 2021. Interventions: Participants were randomized to receive robot-assisted radical cystectomy with intracorporeal reconstruction (n = 169) or open radical cystectomy (n = 169). Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital within 90 days of surgery. There were 20 secondary outcomes, including complications, quality of life, disability, stamina, activity levels, and survival. Analyses were adjusted for the type of diversion and center. Results: Among 338 randomized participants, 317 underwent radical cystectomy (mean age, 69 years; 67 women [21%]; 107 [34%] received neoadjuvant chemotherapy; 282 [89%] underwent ileal conduit reconstruction); the primary outcome was analyzed in 305 (96%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR, 76-84) for patients undergoing robotic surgery vs 80 (IQR, 72-83) for open surgery (adjusted difference, 2.2 days [95% CI, 0.50-3.85]; P = .01). Thromboembolic complications (1.9% vs 8.3%; difference, -6.5% [95% CI, -11.4% to -1.4%]) and wound complications (5.6% vs 16.0%; difference, -11.7% [95% CI, -18.6% to -4.6%]) were less common with robotic surgery than open surgery. Participants undergoing open surgery reported worse quality of life vs robotic surgery at 5 weeks (difference in mean European Quality of Life 5-Dimension, 5-Level instrument scores, -0.07 [95% CI, -0.11 to -0.03]; P = .003) and greater disability at 5 weeks (difference in World Health Organization Disability Assessment Schedule 2.0 scores, 0.48 [95% CI, 0.15-0.73]; P = .003) and at 12 weeks (difference in WHODAS 2.0 scores, 0.38 [95% CI, 0.09-0.68]; P = .01); the differences were not significant after 12 weeks. There were no statistically significant differences in cancer recurrence (29/161 [18%] vs 25/156 [16%] after robotic and open surgery, respectively) and overall mortality (23/161 [14.3%] vs 23/156 [14.7%]), respectively) at median follow-up of 18.4 months (IQR, 12.8-21.1). Conclusions and Relevance: Among patients with nonmetastatic bladder cancer undergoing radical cystectomy, treatment with robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy resulted in a statistically significant increase in days alive and out of the hospital over 90 days. However, the clinical importance of these findings remains uncertain. Trial Registration: ISRCTN Identifier: ISRCTN13680280; ClinicalTrials.gov Identifier: NCT03049410.

Occurrence and Distribution of Heavy Metals in Mining Degraded Soil and Medicinal Plants: A Case Study of Pb/Zn Sulfide Terrain Northern Areas, Pakistan.

Mining activities have serious environmental impacts, thus releasing heavy metals (HMs) such as cadmium (Cd), lead (Pb), chromium (Cr), zinc (Zn) and nickel (Ni) into the surrounding environment. The current paper investigated the impacts of mining activities of Pb-Zn sulfide on soil and medicinal plants. Hence, soil samples (n = 36) and medicinal plants (n = 36) samples were collected, acid extracted and were analyzed through Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for HMs quantification. Our results showed that mineralized zones showed high HMs enrichment levels as compared to non-mineralized zones. Various Indices for HMs assessment revealed that the contaminated soil of the study area had low to extreme level. The mean concentrations of HMs in mining degraded soil and medicinal plants were significantly higher (p ≤ 0.01) and were found in order of Zn > Pb > Cr > Ni > Cd and Cr > Zn > Pb > Ni > Cd respectively. Similarly, some widely consumable medicinal plants showed good metal accumulation for Cd, Cr and Pb i.e., 3.57 mg kg1, 350 mg kg-1 and 335 mg kg-1 in C. sativa, while 5.9 mg kg-1, 276.9 mg kg-1 and 188.7 mg kg-1 in R. hestatus respectively. Hence, the present study recommended that medicinal plants grown in mining areas should be analyzed for HMs concentration before consumption.

Escobar Syndrome with Monodactyly: A Rare Case Report.

Escobar syndrome (nonlethal type of multiple pterygium syndrome) is a very rare genetic disorder. The central manifestations of Escobar syndrome are the presence of multiple pterygia, fixed joint contractures, and characteristic facies. Here, we report a case of Escobar syndrome with additional features such as monodactyly and hypoplastic pectoralis muscle.

The Role of Platelet-Rich Plasma in Reducing Pain, Pruritis, and Improving Wound Healing of Skin Graft Donor Site.

Background Wound healing is a dynamic and complex process. Therefore, no single agent can efficiently mediate all aspects of the wound healing process. Split-thickness graft has become a workhorse of plastic surgery for wound or raw area cover. In this study, we evaluate the effectiveness of autologous platelet-rich plasma (PRP) on the donor site and its effect in pain, purities, and epithelization. Materials and Methods This is a prospective study. A total of 15 patients were included who underwent split skin grafting for burns, trauma, or post-tumor excision raw area. PRP was prepared using standard described procedure. The donor site raw area after harvesting split-thickness graft was measured and the surface area was divided into two equal halves. One half was dressed using PRP and the other half was dressed using paraffin gauze piece only. The dressings were changed weekly for 3 weeks. Observation We found significant reduction in severity of pain and pruritis in the PRP group as compared with control group. Epithelization was faster in the PRP group on day 7 and 14, but the overall healing time was nearly the same by day 21. The side-by-side dressing thus show a definite improvement in the post-split-thickness skin graft wound care and PRP as a good dressing alternative. Conclusion Autologous PRP is very effective adjuvant in management of skin graft donor site. Its role in relieving pain and pruritis over donor site significantly improves patient's discomfort postoperatively. It helps in early and painless wound healing. However, we recommend for larger clinical study for better understanding of the efficacy of this blood product.