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Background: Subarachnoid block is the most commonly used anesthetic technique for lower limb surgeries. Fentanyl is very often combined with hyperbaric bupivacaine as an adjuvant. This study was conducted to compare the block characteristics by administrating bupivacaine and fentanyl in a sequential and premixed manner. Aims and Objectives: The primary objective was to compare the effects of hyperbaric bupivacaine and fentanyl administered either as a premixed solution or sequentially on block characteristics-onset of sensory and motor blockade, regression of block and duration of analgesia. The secondary objective was to study the hemodynamic changes and adverse effects. Materials and Methods: A total of 72 patients scheduled to undergo lower limb surgery were allocated to three groups. Patients in Group A received 15 mg of 0.5 % bupivacaine heavy (H), followed by 25 mcg of fentanyl intrathecally using different syringes. Group B received 25 mcg of fentanyl, followed by 15 mg of 0.5% bupivacaine H in a separate syringe. Group C received premixed 0.5 % bupivacaine H 15 mg and fentanyl 25 mcg in single syringe. The block characteristics-onset and regression of sensory and motor blockade, duration of analgesia, and adverse effects were studied. Results: The mean time (minutes) taken for onset of sensory block was 2.40±0.51 in group A, 4.80±0.53 in Group B and 6.70±0.50 in Group C. Mean time (minutes) taken for onset of motor block was 4.35±0.43 in Group A, while it was 5.64±0.65 and 7.32±0.64 in Groups B and C, respectively. Two segment regression and duration of motor blockade were found to be longer in Group A. Conclusion: Sequential intrathecal administration of bupivacaine followed by fentanyl has a faster onset and prolonged duration of block when compared to the premixed group.

Effective bladder-preserving therapeutic options are needed for patients with bacillus Calmette-Guérin unresponsive non–muscle-invasive bladder cancer. Nadofaragene firadenovec-vncg (Adstiladrin®) was approved by the US Food and Drug Administration as the first gene therapy in urology and the first intravesical gene therapy indicated for the treatment of adult patients with high-risk bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors. The proposed mechanism of action underlying nadofaragene firadenovec efficacy is likely due to the pleiotropic nature of interferon-α and its direct and indirect antitumor activities. Direct activities include cell death and the mediation of an antiangiogenic effect, and indirect activities are those initiated through immunomodulation of the innate and adaptive immune responses. The sustained expression of interferon-α that results from this treatment modality contributes to a durable response. This review provides insight into potential mechanisms of action underlying nadofaragene firadenovec efficacy.

Background: Obstructive sleep apnea (OSA) is a sleep disorder in which the upper airway is partially or completely blocked during sleep. As a result, sleep arousal and arterial oxygen saturation are reduced. According to the epidemiological survey, OAS is relatively common among people that may be associated with psychiatric illnesses. Objectives: The primary objective was to evaluate the stress level among patients suffering from OSA. The secondary objective was to compare the gender preference for stress among patients suffering from OSA. Materials and Methods: A cross-sectional study, approved by the Institutional Ethics Committee, was performed to assess emotional stress among patients suffering from OSA. The study involved 20 participants diagnosed with OSA and reported to the Respiratory Department. The stress levels of the study participants were evaluated with a validated, Perceived Stress Scale (PSS) questionnaire given by the American Sociological Association (ASA). Result: The stress levels presented by the study participants showed that 40% (n = 8) subjects had moderate stress and 60% (n = 12) had severe stress and 30.3% of females depicted emotional stress and 26.2% of males for the same. Conclusion: There is a high psychological stress level among patients suffering from OSA. The females had higher predictions when compared to males. Such patients should be offered an intervention program aimed at stress management to enhance their quality of life.

Objective: Extramammary Paget's disease (EMPD) is a rare cutaneous malignant disease. Due to its rarity, there is a paucity of data regarding best treatment strategy. EMPD primarily affects apocrine gland-bearing skin areas such as the vulva, scrotum, and penis. Our objective was to provide a present-day rationale for diagnosis, pathogenesis, and treatment of EMPD with a focus on recent progress in workup and management of the disease. Methods: Literature on EMPD until February 2022 was assessed through PubMed, MEDLINE databases, and Google scholar. A narrative review of the most relevant articles was provided. Results: EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ. The foundation of EMPD treatment centers around prompt and accurate diagnosis, wide local or Mohs micrographic surgical excision with proper management towards the margin status, and careful consideration for lymphadenectomy in patients with regionally positive disease. Conventional chemotherapies are alternative treatments modality for patients with distant metastases; however, they sometimes have suboptimal efficacy. At present, there is no agreement regarding adjuvant or systemic therapies, although recent studies have shown several insights into the molecular pathogenesis, tumor biology, and genomics of the development and advancement of EMPD, which may lead to novel and targeted treatment approaches for metastatic EMPD in the future. Conclusion: Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling. These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression. Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors, and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

Interferon alpha (IFNα) gene therapy is emerging as a new treatment option for patients with non-muscle invasive bladder cancer (NMIBC). Adenoviral vectors expressing IFNα have shown clinical efficacy treating bacillus Calmette-Guerin (BCG)-unresponsive bladder cancer (BLCA). However, transient transgene expression and adenoviral immunogenicity may limit therapeutic activity. Lentiviral vectors can achieve stable transgene expression and are less immunogenic. In this study, we evaluated lentiviral vectors expressing murine IFNα (LV-IFNα) and demonstrate IFNα expression by transduced murine BLCA cell lines, bladder urothelium, and within the urine following intravesical instillation. Murine BLCA cell lines (MB49 and UPPL1541) were sensitive to IFN-mediated cell death after LV-IFNα, whereas BBN975 was inherently resistant. Upregulation of interleukin-6 (IL-6) predicted sensitivity to IFN-mediated cell death mediated by caspase signaling, which when inhibited abrogated IFN-mediated cell killing. Intravesical therapy with LV-IFNα/Syn3 in a syngeneic BLCA model significantly improved survival, and molecular analysis of treated tumors revealed upregulation of apoptotic and immune-cell-mediated death pathways. In particular, biomarker discovery analysis identified three clinically actionable targets, PD-L1, epidermal growth factor receptor (EGFR), and ALDHA1A, in murine tumors treated with LV-IFNα/Syn3. Our findings warrant the comparison of adenoviral and LV-IFNα and the study of novel combination strategies with IFNα gene therapy for the BLCA treatment.

Urothelial carcinoma accounts for approximately 90% of all bladder cancer diagnoses. Localized, muscle-invasive disease is often managed with a multidisciplinary approach including either neoadjuvant chemotherapy (NAC) followed by radical cystectomy or concurrent chemoradiation, whereas multiple immunotherapies and novel antibody drug conjugates have recently joined platinum-based chemotherapy as standard of care therapy for metastatic disease. However, the clinical trials leading to these standards often require majority if not complete urothelial histology for eligibility. As many as one quarter of patients diagnosed with bladder cancer will have either divergent differentiation of their urothelial carcinoma or an alternate epithelial tumor such as squamous cell carcinoma, adenocarcinoma, or small cell carcinoma; even more rare are non-epithelial tumors such as sarcoma. The rarity of these diseases and their general exclusion from treatment within prospective clinical trials has created a challenging situation where treatment plans are often derived from case series or extrapolated from other disease types and outcomes are poor compared to pure urothelial carcinoma. In this review, we summarize the existing data on the diagnosis and treatment of epithelial, non-urothelial bladder cancers including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma in their localized and advances stages. We will also review the current clinical trial landscape investigating novel approaches to these diseases.

INTRODUCTION: Rhino-orbito-cerebral mucormycosis (ROCM), a life-threatening, acute fungal infection of the nasal cavities and paranasal sinuses, once considered a rare and lethal complication in immunocompromised patients, is now having a massive increase in ROCM incidence in India associated with COVID-19, i.e., COVID-associated mucormycosis with more than 15,000 cases as of May 2021. Early imaging by computed tomography (CT) and magnetic resonance imaging (MRI) is not only helpful in assessing the extent of involvement of this lethal disease but also helps in early diagnosis leading to prompt and aggressive treatment. The present study is aimed at determining and comparing the imaging findings on CT and MRI in ROCM patients, for early diagnosis in suspected cases of ROCM. MATERIALS AND METHODS: The present study is a comparative study of CT and MRI done on 11 patients suspected of ROCM, for 2 months from May to June 2021. RESULTS: Among 11 patients in the study group, ranging from 29 to 65 years of age, 45.4% belonged in 41–60 years of age group, with female predominance. 90.90% cases (10 patients) had maxillary sinus involvement among which 7 cases were diagnosed with ROCM, followed by 63.60% cases (7 patients) had ethmoidal sinus involvement among which 6 cases were diagnosed with ROCM. The involvement of retromaxillary space, pterygopalatine fossa space and masticator space, and cellulitis in premaxillary and preseptal spaces were findings seen only in diagnosed cases of ROCM. Erosions of bones were seen in ROCM cases, 27.20% cases (3 patients) had erosions of walls of maxillary sinus and lamina papyracea each. Orbital involvement in the form of intraconal space and extraocular muscles involvement was seen in 27.20% cases (3 patients) each. Optic nerve involvement was seen in 18.10% cases (2 patients) followed by extraconal space involvement in 9.01% cases (1 patient). Taking KOH staining and/or histopathology (HPR) as standard of reference, CT has a Sensitivity (Sn) of 71.40%, Specificity (Sp) of 100%, Positive predictive value (PPV) of 100%, Negative Predictive Value (NPV) of 66%, and Diagnostic accuracy (DA) of 81% as compared to MRI which has a Sn of 85.7%, Sp of 100%, PPV of 100%, NPV of 80%, and DA of 90.9%. CONCLUSIOIN: CT and MRI play a complementary role in diagnosis of ROCM, as CT is better in detecting bone erosions, whereas MRI is better in detecting soft tissue, orbital and central nervous system involvement. In the acute state of emergency as in the current pandemic with rising cases of ROCM and acute shortage of amphotericin-B, MRI is the single best modality for accurate detection of ROC, helping clinicians in the judicious use of Amphotericin-B.

The high thermal and mechanical inertia of the oceans results in slow changes in sea surface temperatures (SSTs). Changes in SSTs, in turn, can impact atmospheric circulation including water vapor transport, precipitation, and temperatures throughout the world. The Pacific Decadal Oscillation (PDO), the tropical Atlantic SST gradient variability, and the West Pacific Warm Pool are patterns of natural climate variability that tend to persist over decadal time periods. There are current efforts to produce decadal climate predictions, but there is limited understanding if this information can be used in water resources management. Understanding the current state of decadal climate variability (DCV) phenomena and the probability of persisting in that state may be useful information for water managers. This information could improve forecasts that aid operations and short-term planning for reservoir management, domestic and industrial water supplies, flood risk management, energy production, recreation, inland navigation, and irrigation. If conditions indicate a higher likelihood of drought, reservoir managers could reduce flood storage space and increase storage for conservation purposes. Improved forecasts for irrigation could result in greater efficiencies by shifting crops and rotational crop patterns. The potential benefits of using a forecast must be balanced against the risk of damages if the forecast is wrong. Seasonal forecasts using DCV information could also be used to inform drought triggers. If DCV indices indicate that the climate has a higher probability of dry conditions, drought contingency plans could be triggered earlier. Understanding of DCV phenomena could also improve long-range water resources planning. DCV can manifest itself in relatively short-term hydrologic records as linear trends that complicate hydrologic frequency analysis, which has traditionally assumed that hydrologic records are stationary. HIGHLIGHTS Knowledge of the current phase of decadal climate variability (DCV) indices and the probability of persisting in that state may be useful information for water managers for seasonal forecasts.; DCV information could inform the allocation of flood storage and conservation storage spaces in reservoirs, but the potential use of DCV information depends on the risk if the forecasts are wrong.; Analysis of DCV phenomena could help explain trends and breakpoints in nonstationary flood frequency analysis.;

PurposeSarcopenia is associated with decreased survival and increased complications in patients with renal cell carcinoma. Readily identifying patients with low muscle composition that may experience worse outcomes or would benefit from preoperative intervention is of clinical interest. Traditional body composition analysis methods are resource intensive; therefore, linear segmentation with routine imaging has been proposed as a clinically practical alternative. This study assesses linear segmentation’s prognostic utility in nonmetastatic renal cell carcinoma.Materials and MethodsA single institution retrospective analysis of patients that underwent nephrectomy for nonmetastatic renal cell carcinoma from 2005-2021 was conducted. Linear segmentation of the bilateral psoas/paraspinal muscles was completed on preoperative imaging. Total muscle area and total muscle index associations with overall survival were determined by multivariable analysis.Results532 (388 clear cell) patients were analyzed, with median (IQR) total muscle index of 28.6cm2/m2 (25.8-32.5) for women and 33.3cm2/m2 (29.1-36.9) for men. Low total muscle index was associated with decreased survival (HR=1.96, 95% CI 1.32-2.90, p

Abstract Background Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT. Methods Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm. Discussion To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.

We find that critical factors affecting real estate project decisions can vary while market changes in the city of Ahmedabad have led to the majority of landmark buildings facing obsolesce, redevelopment and spatial redundancy. Case studies can assist in data collection in the cultural context and accommodate indirect observations of the variables analyzed in the early stages of research (Teegavarapu & Summers, 2008; Rowley, 2002). Decisions have led to capital losses for some, while bringing about profitable opportunities for developers who take timely risks.

Background. Dental porcelain has excellent esthetics in combination with biocompatibility and is one of the most commonly used restorative materials. Its low tensile strength remains a major drawback. The porcelain-fused-to-metal restorations have been introduced to increase the fracture resistance of dental porcelain. The aim of this study was to evaluate the effect of different surface treatments on the bond strength of a non-precious alloy to ceramic. Methods. The present cross-sectional observational study was conducted with forty samples of cobalt‒chromium that were fabricated with porcelain interposed between the two metal test pieces. The metal was subjected to combinations of different surface treatments. The samples group A (n=10) were not subjected to any surface treatments. Group B samples underwent sandblasting and surface grinding. Group C samples were subjected to sandblasting, surface grinding and degassing; and group D samples underwent sandblasting, surface grinding, ultrasonic cleaning and degassing. The tensile bond strength was measured in a universal testing machine, and a scanning electron microscope (SEM) was used to obtain images of the samples after surface treatment to determine the surface irregularities and after the debonding of the samples for the type of the bond failure. ANOVA was used for the statistical analysis. Results. The results showed significant variations in the tensile bond strength between the four groups (F=251.05, P=0.000). The SEM images of group A showed no surface irregularities; group C samples exhibited surface irregularities more than those in group B. Group D had the highest surface irregularities. SEM evaluations showed a statistically significant difference in the type of bond failure (P

Spontaneous regression of histologically proven squamous cell carcinoma is extremely rare. We present the case of a 66-year-old male with histologically proven squamous cell carcinoma of the larynx which regressed spontaneously without any treatment. The patient is alive and healthy 3 years after the diagnosis. The exact mechanisms of spontaneous regression remain elusive although spontaneous regression is not the natural course of squamous cell carcinoma and the disease may recur in time and space.

Abstract Acute myeloid leukemia (AML) is a heterogenous disease associated with distinct genetic and molecular abnormalities. Somatic mutations result in dysregulation of intracellular signaling pathways, epigenetics, and apoptosis of the leukemia cells. Understanding the basis for the dysregulated processes provides the platform for the design of novel targeted therapy for AML patients. The effort to devise new targeted therapy has been helped by recent advances in methods for high-throughput genomic screening and the availability of computer-assisted techniques for the design of novel agents that are predicted to specifically inhibit the mutant molecules involved in these intracellular events. In this review, we will provide the scientific basis for targeting the dysregulated molecular mechanisms and discuss the agents currently being investigated, alone or in combination with chemotherapy, for treating patients with AML. Successes in molecular targeting will ultimately change the treatment paradigm for the disease.

The loss of continuity of the lower jaw following surgical excision destroys the balance and symmetry of mandibular functions. Prosthodontic rehabilitation has, therefore, become the treatment option to restore functions, aesthetics and to alleviate psychological status in such patients who deny further surgical intervention or in whom surgical reconstruction procedures are not indicated. This case report describes a prosthodontic rehabilitation of a patient who has undergone a hemimandibulectomy with the overlay denture lined with the silicone liner to fulfil the patient’s needs and requirements.

Hemoglobin (Hb) Sherwood Forest is a rare high-affinity hemoglobin first described in 1977, arising from an Arg to Thr substitution at codon 104 of the beta chain. This hemoglobin variant has been identified in few individuals and has been associated with a compensatory erythrocytosis in the homozygous state. Prior scarce case reports have noted that heterozygotes for this variant are phenotypically normal. Here we present a patient who was evaluated in our hematology clinic for chronic erythrocytosis and was found to be heterozygous for Hb Sherwood Forest. No other primary or secondary cause of his polycythemia was identified. This is the first described case of heterozygous Hemoglobin Sherwood Forest causing erythrocytosis.

Decision makers in drought-prone regions of the world and in international organizations responsible for drought relief require advance information, preferably on the decadal timescale, of future hydro-meteorological conditions. Focusing on Southern Africa (SA), a region subject to droughts, we used indices of four decadal climate variability phenomena, statistically associated with Self-calibrating Palmer Drought Severity Index (SC-PDSI), hindcast/forecast by the MIROC5 Earth System Model from 1961 to 2019–2020, in a statistical prediction system (SPS) to assess SC-PDSI predictability. The SA-averaged correlation coefficient between hindcast and observations-based SC-PDSI increased from 0.2 in the 1980s to 0.33 in the 2001 to 2009–2010 period; grid point correlations within SA increased from 0.4 to over 0.7 during the last 30 years. The MIROC5 – SPS system forecasts that SA may experience a moderate drought from 2014 to 2016, followed by a wet period around 2019. These hydrologic event forecasts are predicated on the absence of major low-latitude volcanic eruptions during the prediction period.

2D-gel electrophoresis (2DGE) is an important technique in proteomics for analyzing the protein expressions. However, the analysis of 2DGE images is still a cumbersome and tedious task. One of the main reasons is the presence of a large amount of the inhomogeneities in the foreground and the background intensities. In this paper, we have proposed a novel approach of segmentation of the protein spots in the non separable wavelet domain. It utilizes the inter-scale relationship among enhanced wavelet coefficients, which can easily distinguish the different features of the image—the interior region of spots, the edges and the background. This technique is based on a single threshold and is independent of the gray value of the image. It copes with the inhomogeneities in the 2DGE images up to a great extent, which is helpful for finding the protein spots accurately. The artifacts are further removed using a non-threshold based method comprising a weighted Gaussian energy distribution model. Experimental results show that our method outperforms the available commercial software and previously reported works. [ABSTRACT FROM AUTHOR]