Chronic pain, chronic stress and substance use: overlapping mechanisms and implications.

Chronic pain is among the most common reasons adults in the U.S. seek medical care. Despite chronic pain's substantial impact on individuals' physical, emotional, and financial wellness, the biologic underpinnings of chronic pain remain incompletely understood. Such deleterious impact on an individuals' wellness is also manifested in the substantial co-occurrence of chronic stress with chronic pain. However, whether chronic stress and adversity and related alcohol and substance misuse increases risk of developing chronic pain, and, if so, what the overlapping psychobiological processes are, is not well understood. Individuals suffering with chronic pain find alleviation through prescription opioids as well as non-prescribed cannabis, alcohol, and other drugs to control pain, and use of these substances have grown significantly. Substance misuse also increases experience of chronic stress. Thus, given the evidence showing a strong correlation between chronic stress and chronic pain, we aim to review and identify overlapping factors and processes. We first explore the predisposing factors and psychologic features common to both conditions. This is followed by examining the overlapping neural circuitry of pain and stress in order to trace a common pathophysiologic processes for the development of chronic pain and its link to substance use. Based on the previous literature and our own findings, we propose a critical role for ventromedial prefrontal cortex dysfunction, an overlapping brain area associated with the regulation of both pain and stress that is also affected by substance use, as key in the risk of developing chronic pain. Finally, we identify the need for future research in exploring the role of medial prefrontal circuits in chronic pain pathology. Critically, in order to alleviate the enormous burden of chronic pain without exacerbating the co-occurring substance misuse crisis, we emphasize the need to find better approaches to treat and prevent chronic pain.

Dietary Methionine and Total Sulfur Amino Acid Restriction in Healthy Adults.

OBJECTIVES: Dietary restriction of methionine (Met) and cysteine (Cys) delays the aging process and aging-related diseases, improves glucose and fat metabolism and reduces oxidative stress in numerous laboratory animal models. Little is known regarding the effects of sulfur amino acid restriction in humans. Thus, our objectives were to determine the impact of feeding diets restricted in Met alone (MetR) or in both Met and Cys (total sulfur amino acids, SAAR) to healthy adults on relevant biomarkers of cardiometabolic disease risk. DESIGN: A controlled feeding study. SETTING AND PARTICIPANTS: We included 20 healthy adults (11 females/9 males) assigned to MetR or SAAR diet groups consisting of three 4-wk feeding periods: Control period; low level restriction period (70% MetR or 50% SAAR); and high level restriction period (90% MetR or 65% SAAR) separated by 3-4-wk washout periods. RESULTS: No adverse effects were associated with either diet and level of restriction and compliance was high in all subjects. SAAR was associated with significant reductions in body weight and plasma levels of total cholesterol, LDL, uric acid, leptin, and insulin, BUN, and IGF-1, and increases in body temperature and plasma FGF-21 after 4 weeks (P<0.05). Fewer changes occurred with MetR including significant reductions in BUN, uric acid and 8-isoprostane and an increase in FGF-21 after 4 weeks (P<0.05). In the 65% SAAR group, plasma Met and Cys levels were significantly reduced by 15% and 13% respectively (P<0.05). CONCLUSION: These results suggest that many of the short-term beneficial effects of SAAR observed in animal models are translatable to humans and support further clinical development of this intervention.

Plasmonic Copper-activated ZnO Microarrays for Efficient Photoelectrocatalytic Applications.

In the present work, green synthesized plasmonic copper nanostructures derived from carbon quantum dots (PCQDs) activated ZnO microarrays (MAs) based catalyst system is developed and studied for photocatalytic activity and photoelectrocatalytic water splitting. CQDs are synthesized from pharmaceutical waste and used as a reducing agent to synthesize PCQDs of an average size of 10±2 nm. PCQDs decorated ZnO (PCQDs/ZnO) MAs exhibited enhanced photocurrent density of ∼7.1 mA/cm2 at 1.23 V (vs. RHE), which is ∼11 fold to ZnO MAs alone (0.65 mA/cm2 ). The catalyst exhibits an ABPE of 1.07% at 0.7 V (vs. RHE), IPEC of 8.8% for 450 nm, and hydrogen production rate of 435 µmol/h. The enhanced PEC characteristics are assigned to the improved photons collection and better charge transfer for their participation in oxidation/reduction reaction. The same is well supported with DFT studies for the PCQDs/ZnO MAs catalyst for the first time.

Lesion Border Detection of Skin Cancer Images Using Deep Fully Convolutional Neural Network with Customized Weights.

Deep learning techniques have been widely employed in semantic segmentation problems, especially in medical image analysis, for understanding image patterns. Skin cancer is a life-threatening problem, whereas timely detection can prevent and reduce the mortality rate. The aim is to segment the lesion area from the skin cancer image to help experts in the process of deeply understanding tissues and cancer cells' formation. Thus, we proposed an improved fully convolutional neural network (FCNN) architecture for lesion segmentation in dermoscopic skin cancer images. The FCNN network consists of multiple feature extraction layers forming a deep framework to obtain a larger vision for generating pixel labels. The novelty of the network lies in the way layers are stacked and the generation of customized weights in each convolutional layer to produce a full resolution feature map. The proposed model was compared with the top four winners of the International Skin Imaging Collaboration (ISIC) challenge using evaluation metrics such as accuracy, Jaccard index, and dice co-efficient. It outperformed the given state-of-the-art methods with higher values of the accuracy and Jaccard index.

Effects of Momordica Charantia (Karela/bitterguord) in Type 2 Diabetic Patients Taking Allopathic Drugs: A pilot study.

Background Momordica charantia is evoloving as supplementary therapy in type 2 diabetes mellitus. Animal studies reveal its anti-diabetic and lipid lowering property. However, clinical studies with human subjects are very few. Objective To find out the effects of Momordica charantia supplements on glycemic and lipid profile among type 2 diabetes mellitus patients taking allopathic drugs. Method A comparative study was conducted in internal medicine department of B P Koirala Institute of Health Sciences, Dharan from July 2015 to May 2016 after ethical clearance. Twenty two uncomplicated type-2 diabetes mellitus patients were enrolled. Group A patients were supplemented with allopathic drug (oral anti-diabetic agents) only and Group B with add on treatment of 200 ml juice of Momordica charantia along with allopathic drug daily for ninety days. Fasting, post prandial blood sugar and lipid profile levels were compared between baseline and ninety days post supplementation. Data was collected and entry was done in Statistical Packages for Social Services version 20.0, using independent t test with p < 0.05. Result Add on treatment with 200 ml of Momordica charantia along with anti-diabetic drug daily significantly reduced fasting (p= < 0.0001) and post prandial blood sugar (p < 0.0001). Treatment with anti-diabetic drugs only reduced fasting (p = 0.0008) and post-prandial blood sugar but the reduction was not significant ((p =0.0001). There was improvement in lipid profile by both anti-diabetic drugs alone and Momordica charantia along with anti-diabetic drug, but it was not significant. Conclusion Add on treatment with 200 ml/day juice of Momordica charantia is effective in glycaemic control in type-2 diabetes mellitus patients as compared to the allopathic treatment alone.

Follow-up of colorectal cancer and patterns of recurrence.

Colorectal cancer is one of the commonest cancers detected as also amongst the most common causes of cancer death. Survival has improved due to better disease understanding and treatment; however, a substantial proportion of patients recur after curative intent therapy. In this article, we will discuss the imaging features of recurrent colorectal cancer and the role of the radiologist in its management.

Direct visualization and correlation of liver stereotactic body radiation therapy treatment delivery accuracy with interfractional motion.

This study used the visualization of hypo-intense regions on liver-specific MRI to directly quantify stereotactic body radiation therapy (SBRT) spatial delivery accuracy. Additionally, the interfractional motion of the liver region was determined and compared with the MRI-based evaluation of liver SBRT spatial treatment delivery accuracy. Primovist® -enhanced MRI scans were acquired from 17 patients, 8-12 weeks following the completion of liver SBRT treatment. Direct visualization of radiation-induced focal liver reaction in the form of hypo-intensity was determined. The auto-delineation approach was used to localize these regions, and center-of-mass (COM) discrepancy was quantified between the MRI hypo-intensity and the CT-based treatment plan. To assess the interfractional motion of the liver region, a planning CT was registered to a Cone Beam CT obtained before each treatment fraction. The interfractional motion assessed from this approach was then compared against the localized hypo-intense MRI regions. The mean ± SD COM discrepancy was 1.4 ± 1.3 mm in the left-right direction, 2.6 ± 1.8 mm in an anteroposterior direction, and 1.9 ± 2.6 mm in the craniocaudal direction. A high correlation was observed between interfractional motion of visualized hypo-intensity and interfractional motion of planning treatment volume (PTV); the quantified Pearson correlation coefficient was 0.96. The lack of correlation was observed between Primovist® MRI-based spatial accuracy and interfractional motion of the liver, where Pearson correlation coefficients ranged from -0.01 to -0.26. The highest random and systematic errors quantified from interfractional motion were in the craniocaudal direction. This work demonstrates a novel framework for the direct evaluation of liver SBRT spatial delivery accuracy.

A prospective longitudinal study to evaluate bone health, implication of FRAX tool and impact on quality of life (FACT-P) in advanced prostate cancer patients.

BACKGROUND: Androgen-deprivation therapy (ADT) as a treatment modality in advanced prostate cancer has deleterious effect on bone mineral density (BMD) and quality of life (QOL). Using FRAX (Fracture Risk Assessment) model, candidates at high risk of fractures can be predicted and appropriate treatment can be initiated at early step to prevent skeletal-related events. Objectives of the present study were to evaluate bone health, implication of FRAX tool in advanced prostate cancer and to see the impact of ADT and Bone-directed therapy (BDT) on FRAX and FACT-P QOL scores. MATERIAL & METHOD: We conducted a prospective longitudinal study of 83 localized and metastatic prostate cancer patients from March 2017 to Dec 2020. FRAX tool using BMD femoral neck (GE-Lunar) was used to compute the probability of 10-year Major osteoporotic fracture (MOF) and hip fracture risk %. Patients who received monthly Zolendronic acid with or without Vitamin-D/calcium supplementation were classified as BDT group. FRAX and FACT-P were measured at baseline and 12 months follow-up and compared between different therapeutic modalities to see the impact on clinical outcomes. RESULTS: Majority of patients had skeletal metastasis (78.3%) and high-grade disease at presentation. Secondary osteoporosis was the most commonly (82.05%) observed clinical risk factor (CRF) followed by smoking (19.23%). Hip fracture risk ≥3% accounted for larger proportion of patients than did MOF risk ≥20% (21.2% and 2.5%, respectively). Statistically significant reduction was observed in both MOF and hip fracture risk in BDT group, while worsening on ADT. ADT duration correlated positively with both MOF and hip fracture risk (R2=0.148, P<0.001 and R2=0.164, P<0.001, respectively). FRAX score accurately predict future fracture events in majority (80%) of high-risk patients. Statistically and clinically significant worsening in PWB, EWB, PCS, FACT-P Total, FACT-P TOI and FAPSI scores were observed in patients on ADT. Statistically and clinically significant improvement was noted in physical well-being in BDT group. However, other QOL domains and FACT-P total scores remained stable. CONCLUSIONS: ADT caused duration depended worsening of FRAX and FACT-P score in these patients while improvements of FRAX were seen on BDT. FRAX tool is advantageous in identifying the patients who require early intervention or therapy to decrease skeletal-related events.

Critical Role of 3D ultrasound in the diagnosis and management of Robert's uterus: a single-centre case series and a review.

A septate uterus with a non-communicating hemicavity was first described by Robert in 1969/70 as a specific malformation of the uterus. The condition is commonly associated with a blind uterine hemicavity, unilateral haematometra, a contralateral unicornuate uterine cavity and a normal external uterine fundus. The main symptoms are repetitive attacks of pain at four-weekly intervals around menarche, repeated dysmenorrhea, recurrent pregnancy loss and infertility. In this report, we review the disease, its diagnosis and treatment, and describe five cases of Robert's uterus. Three dimensional (3D) ultrasound (US) imaging was performed by the transvaginal route in four cases. In the fifth case of a 13-year-old girl, we avoided the vaginal route and magnetic resonance imaging (MRI) and 3D transrectal US yielded the correct diagnosis. The following treatment procedures were undertaken: laparoscopic endometrectomy, hysteroscopic septum resection, laparoscopic uterine hemicavity resection and total laparoscopic hysterectomy (TLH). The diagnosis and optimum treatment of Robert's uterus remains difficult for clinicians because of its rarity. A detailed and careful assessment by 3D US should be performed, followed by hysteroscopy in combination with laparoscopy, to confirm the diagnosis.

Effect of core hydrophobicity on the electrophoresis of pH-regulated soft particles.

We propose a theoretical study on the electrophoresis of core-shell composite soft particles considering the effect of hydrodynamic slip length of the hydrophobic inner core. The surface of the inner core as well as the soft polymeric shell bear zwitterionic functional groups and the charged conditions depend on the nearby micro-environment. Within a low potential and weak electric field framework, the mathematical equations of the generalized electrokinetic theory for soft surfaces are solved analytically subject to appropriate boundary conditions, and a general electrophoretic mobility expression in an integral form involving the pH-dependent electrostatic potential is derived. With the help of suitable numerical schemes, electrophoretic mobility can easily be obtained. The effect of hydrophobicity of the inner core on the electrophoretic mobility of pH-regulated soft particles is illustrated for a wide range of pertinent parameters.

Diagnostic Relevance of GATA 3 Expression in Urinary Bladder Carcinoma of Divergent Differentiation and Other Histological Variants.

GATA binding protein 3, a zinc finger transcription factor, has now been demonstrated as a valuable and sensitive marker for conventional urothelial carcinoma with sparse literature related to its expression in various histological variants. It is a prospective study where 74 consecutive cases of bladder carcinoma were included between August 2016 and January 2017 followed by immunohistochemistry to assess GATA 3 expression in conventional as well as different urothelial carcinoma (UC) variants. Overall, 57 of the 74 lesions (77%) demonstrated nuclear staining for GATA 3. GATA 3 expression significantly correlated with histological grade (P < 0.001) and muscle invasion (P = 0.005). Divergent differentiation was observed in 54% (40/74) of the total cases. The study included 12 different variants of urothelial carcinoma. All or majority of the cases of clear cell (6/6, 100%), glandular (6/8, 75%), and sarcomatoid (4/6, 66.7%) variants expressed GATA 3 in a moderate to strong fashion and belonged to group III or IV. Nested variant, small cell carcinoma, pure squamous cell carcinoma, and squamous component of urothelial carcinoma with squamous differentiation do not show any GATA 3 expression. GATA 3 was expressed more intensely as well as in greater number of tumor cells at lymph node metastatic tumor deposits as compared to the primary tumor. GATA 3 expression was not significantly associated with tumor stage or patients' clinical outcomes. GATA 3 is expressed in majority of variants of UC albeit with variable staining; however, situation is challenging in some variants known to be associated with poor prognosis like nested variant, small cell carcinoma, and squamous cell carcinoma where it is not expressed. Hence, the sensitivity of this determinant is diminished in these variants, which may affect the interpretation of GATA 3 stains at metastatic sites as well as their distinction from secondary bladder involvement, by tumors of non-urothelial origin.

Electrophoresis of dielectric and immiscible-liquid-layer-encapsulated colloids in aqueous media.

In this paper we consider the electrophoresis of a functionalized nanoparticle in electrolyte solution. The undertaken particle is comprised of a rigid inner core encapsulated with a layer of dielectric liquid (e.g., oil or lipid layer), which is immiscible to the bulk aqueous medium. The peripheral liquid layer of the undertaken nanoparticle contains mobile charges due to presence of solubilized surfactants. The mobile electrolyte ions can penetrate across the peripheral layer depending on the difference in the Born energy of the both phases. Such types of nanoparticles have received substantial attention due to their widespread applications in biomedical research. The electric double layer (EDL) is governed by the linearized Poisson-Boltzmann equation under a low potential limit and the electroosmotic flow field is governed by modified Stokes equation. We adopt the flat-plate formalism to obtain the closed analytical expression for the electrophoretic mobility of the undertaken particle under a thin EDL approximation. The dependence of electrophoretic mobility on the pertinent parameters is also illustrated.

The impact of ultrasound in an integrated one-stop sarcoma clinic.

AIM: To evaluate the utilisation of ultrasound within a one-stop clinic model in a regional bone and soft-tissue sarcoma centre in the UK, assess its contribution to patient management, and compare diagnostic outcomes to general musculoskeletal "lumps and bumps" clinics. MATERIALS AND METHODS: This study was a retrospective evaluation of 1,918 referrals between October 2016 and September 2018. All ultrasound examinations and biopsies were performed by one of two musculoskeletal sarcoma radiologists. Ultrasound criteria for suspicion of malignancy were agreed. Study parameters included patient demographics, imaging modality, imaging findings, biopsy results, and time intervals. Correlation has been made between imaging findings and biopsy results. RESULTS: Five hundred and twenty-four patients (27%) underwent diagnostic ultrasound within the one-stop clinic, out of which 244 (46.5%) underwent an ultrasound-guided biopsy within the same appointment. From this cohort, 412 (78.6%) were given a likely benign diagnosis, either based on imaging alone or in combination with an ultrasound-guided biopsy and a histologically malignant diagnosis was made in the remaining 112 (21.4%). Diagnostic ultrasound within the one-stop sarcoma clinic has a positive predictive value of 86%, negative predictive value of 97%, and sensitivity of 89%. CONCLUSION: Integration of ultrasound within a one-stop sarcoma clinic provides rapid diagnostic imaging input within the outpatient setting and facilitates early effective triaging of patients into appropriate management plans. It reduces waiting times, unnecessary outpatient appointments and short-term patient anxiety. Clinical and communications skills of the sarcoma radiologist are of paramount importance to improving overall efficiency and patient experience.

TiO2 nanofibres decorated with green-synthesized PAu/Ag@CQDs for the efficient photocatalytic degradation of organic dyes and pharmaceutical drugs.

Organic pollutants such as dyes and pharmaceutical drugs have become an environmental menace, particularly in water bodies owing to their unregulated discharge. It is thus required to develop an economically viable and environment-friendly approach for their degradation in water bodies. In this study, for the first time, we report green route-synthesized plasmonic nanostructures (PM-CQDs (where M: Au and Ag)) decorated onto TiO2 nanofibers for the treatment of toxic dye- and pharmaceutical drug-based wastewater. PM-CQDs are efficaciously synthesized using carbon quantum dots (CQDs) as the sole reducing and capping agent, wherein CQDs are derived via a green synthesis approach from Citrus limetta waste. The characteristic electron-donating property of CQDs played a key role in the reduction of Au3+ to Au0 and Ag+ to Ag0 under visible light irradiation to obtain PAu-CQDs and PAg-CQDs, respectively. Thus, the obtained CQDs, PAu-CQDs, and PAg-CQDs are loaded onto TiO2 nanofibers to obtain a PM-CQD/TiO2 nanocomposite (NC), and are further probed via transmission electron microscopy, scanning electron microscopy and UV-visible spectrophotometry. The degradation of organic pollutants and pharmaceutical drugs using methylene blue and erythromycin as model pollutants is mapped with UV-vis and NMR spectroscopy. The results demonstrate the complete MB dye degradation in 20 minutes with 1 mg mL-1 of PAu-CQD/TiO2 NC, which otherwise is 30 minutes for PAg@CQD/TiO2 dose under visible light irradiation. Similarly, the pharmaceutical drug was found to degrade in 150 minutes with PAu-CQD/TiO2 photocatalysts. These findings reveal the enhanced photocatalytic performance of the green-synthesized Au decorated with TiO2 nanofibers and are attributed to the boosted SPR effect and aqueous-phase stability of Au nanostructures. This study opens a new domain of utilizing waste-derived and green-synthesized plasmonic nanostructures for the degradation of toxic/hazardous dyes and pharmaceutical pollutants in water.

Optimising MRI small bowel techniques.

Magnetic resonance imaging (MRI)-based techniques have emerged as the preferred technique for the diagnostic evaluation of the small intestine, particularly in the adult population. The lack of ionising radiation makes MRI ideal for use in younger patients or in cases that require repeated follow-up investigations. Imaging of the small intestine may be carried out using the intubation (enteroclysis) or the ingestion (enterography) techniques. Enterography examinations are more acceptable to patients and may provide similar diagnostic accuracy compared to intubation methods. In this review, methods of improving and optimising MRI of the small intestine are described.