Efficacy and safety of abemaciclib alone and with PI3K/mTOR inhibitor LY3023414 or galunisertib versus chemotherapy in previously treated metastatic pancreatic adenocarcinoma: A randomized controlled trial.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDAC) are characterized by frequent cell cycle pathways aberrations. This study evaluated safety and efficacy of abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, as monotherapy or in combination with PI3K/mTOR dual inhibitor LY3023414 or TGFß inhibitor galunisertib versus standard of care (SOC) chemotherapy in patients with pretreated metastatic PDAC. METHODS: This Phase 2 open-label study enrolled patients with metastatic PDAC who progressed after 1-2 prior therapies. Patients were enrolled in a safety lead-in (abemaciclib plus galunisertib) followed by a 2-stage randomized design. Stage 1 randomization was planned 1:1:1:1 for abemaciclib, abemaciclib plus LY3023414, abemaciclib plus galunisertib, or SOC gemcitabine or capecitabine. Advancing to Stage 2 required a disease control rate (DCR) difference ≥0 in abemaciclib-containing arms versus SOC. Primary objectives for Stages 1 and 2 were DCR and progression-free survival (PFS), respectively. Secondary objectives included response rate, overall survival, safety, and pharmacokinetics. RESULTS: One hundred and six patients were enrolled. Abemaciclib plus galunisertib did not advance to Stage 1 for reasons unrelated to safety or efficacy. Stage 1 DCR was 15.2% with abemaciclib monotherapy, 12.1% with abemaciclib plus LY3023414, and 36.4% with SOC. Median PFS was 1.7 months (95% CI: 1.4-1.8), 1.8 months (95% CI: 1.3-1.9), and 3.3 months (95% CI: 1.1-5.7), respectively. No arms advanced to Stage 2. No new safety signals were identified. CONCLUSION: In patients with pretreated metastatic PDAC, abemaciclib-based therapy did not improve DCRs or PFS compared with SOC chemotherapy. No treatment arms advanced to Stage 2. Abemaciclib remains investigational in patients with PDAC.

Unusual Clinical Presentation of Nephrotic Syndrome With Significant Renal Vein Thrombosis in a Young Male: A Case Report and Literature Review.

Primary membranous glomerulopathy is the most common cause of idiopathic nephrotic syndrome, with increasing recognition as an autoimmune-mediated disease. We present the case of a 31-year-old Hispanic male with no prior medical or family history, presenting with one month of dyspnea on exertion, lower extremity, and periorbital edema with a recent diagnosis of pulmonary embolism. Upon further imaging, renal vein thrombosis was discovered with significant lab dysfunction concerning nephrotic syndrome. Further, a workup of kidney biopsy and serum antibody levels revealed the cause to be anti-phospholipase A2 receptor (PLA2R)-mediated.

A 7-Year Retrospective Analysis of Titanium Plates Removal Following Orthognathic Surgery.

Objective: The aim of this study was to investigate the incidence of plate removal in orthognathic surgery patients and the reasons for their removal and to potentially identify the factors that may contribute to it. Methods: A retrospective study included all patients who underwent orthognathic surgery at Selayang Hospital from January 2011 to December 2017. The variables of interest recorded included patient age, gender, the existing skeletal deformity, type of surgery undertaken and number and location of plates inserted and removed. In addition, the reasons for plate removal and duration between plate insertion and removal were also recorded. Results: Ninety-seven patients with a mean age of 21.33 were included in the study. Nine patients with total of 33 plates had their miniplate fixation removed. Three patients underwent bi-maxillary surgery, and six patients underwent BSSO. The average time from insertion to removal was 22.33 months. The reasons for removal included pain, palpable and exposed plates, infection and on patient request. Conclusion: We report a 9.28% incidence of plate removal in patients who undergo orthognathic surgery which is comparable to the existing literature.

Cadmium phytoremediation potential of Brassica genotypes grown in Cd spiked Loamy sand soils: Accumulation and tolerance.

Phytoremediation acts as an efficient methodology for management of toxic elements spiked soils. The accumulation and tolerance potential of hyper-accumulator plants for toxic elements act as an index for in-situ removal of toxic elements. Extraction of cadmium (Cd) through its accumulation in harvestable parts of plants has attracted attention as the economic and environment friendly technique. Brassica genotypes have greater potential to accumulate Cd when grown in Cd spiked soils. Therefore, for evaluation of comparative efficiency of three Brassica genotypes (B. juncea, B. campestris and B. napus) in phytoremediation of Cd spiked soils, a pot study was carried out in Cd contaminated soil with 6 levels as 0, 5, 10, 20, 40, and 80 mg kg-1 soil. Results indicated that dry biomass production of Brassica genotypes declined with the enhanced Cd contamination in soil. The reduction in grain and shoot yield varied from 2.87 to 1.85 and 11.85 to 8.00 g pot-1 with increased Cd contamination from 5 to 80 mg kg-1 soil. Similarly, increased levels of Cd contamination resulted in enhanced concentration and accumulation in grains as well as shoots of all Brassica genotypes. Among Brassica genotypes, B. juncea recorded the highest production of dry biomass (12.8 g pot-1), Cd accumulation (736.0 µg pot-1). Also, the bioaccumulation coefficient and tolerance index indicated that B. juncea is the most tolerant genotype to Cd contamination in soil. Therefore, B. juncea could act as the most potential genotypes for decontamination of Cd spiked soils by preventing its entry into food chain.

The Contribution of Galenics to Patients' Sensory Perception of Nasal Sprays After Nasal Surgery: Data from a Prospective Randomised, Controlled, Double-Blind, Crossover, Multicentre Study.

INTRODUCTION: Postoperative care after nasal surgery is commonly achieved with nasal sprays. The current study compared two decongesting, wound-healing nasal sprays in patients after nasal surgery in order to investigate their sensory perception. One of the sprays was a new galenic formulation (nasic® neo, Cassella-med GmbH & Co. KG). METHODS: According to the crossover design, patients who had undergone nasal surgery applied two different nasal sprays during two treatment periods of 4 days each, interrupted by a 3-day washout period. Sensory perception of the nasal sprays was assessed with the nasal spray sensoric scale. Throughout the study, nasal obstruction was evaluated by patients, and physical examinations, measurements of vital parameters and rhinoscopic examinations were carried out by investigators. Adverse events were documented during the entire study, and following treatment, patients judged the overall preference, efficacy and tolerability of both products. RESULTS: Overall, no significant differences in sum scores of the assessments of the nasal spray sensoric scale were observed between treatments. A significant period effect observed during the crossover study limited the overall analysis. Nevertheless, significantly more patients preferred the new galenics nasal spray compared to the comparator spray (57.1% vs. 34.7%; p = 0.031). Further, 10% more patients rated the efficacy of the new galenics as 'good' to 'very good' compared to the comparator. Importantly, a subgroup population of patients with more pronounced signs of inflammation present at screening evaluated the sensory perception of the new galenics as significantly better (p = 0.033) compared to the comparator. Within this subgroup, no period effect was observed. The application of both nasal sprays was shown to be safe and well-tolerated. CONCLUSION: The overall sensory perception of both nasal sprays was evaluated comparably well in patients after nasal surgery and overall the application of the new galenics nasal spray was preferred by significantly more patients compared to the comparator nasal spray. Patients with marked nasal abnormalities may have a greater benefit from the contribution of galenics as significant differences in the sensory evaluation by the nasal spray sensoric scale in favour of the new galenics product were shown for this subgroup. TRIAL REGISTRATION: The current study was registered in the EU Clinical Trials Register with the EudraCT No. 2019-004936-52.

Avoidance behavior of Eisenia fetida and Metaphire posthuma towards two different pesticides, acephate and atrazine.

The avoidance behavior is regarded as the method that provides first hand information about the behavior of an organism in the presence of contaminants in the soil. Very little data is found in literature regarding the effect of pesticides on tropical earthworms. Two pesticides, acephate and atrazine which are widely used in Indian tropical area were investigated for their avoidance behavior on standard species, E. fetida (ISO 2007) and on a tropical species, M. posthuma. The avoidance tests are rarely replicated on tropical species, M. posthuma in comparison to standard species, E. fetida or E. andrei. The standard avoidance test (ISO 2007) was taken into consideration for two different species of earthworm. Significant difference in the distribution of earthworms in the control and test soils was found depicting that soil composition plays a vital role in affecting the distribution of worms. The results also show higher sensitivity of E. fetida in comparison to M. posthuma in terms of avoidance response for both the pesticides. For risk assessment, the soil types and indigenous soil species of earthworms must be taken into consideration for evaluation of soil contamination. Avoidance tests forms the basis to study the molecular mechanisms underlying the receptor proteins responsible for the process of chemesthesis in annelids.

Fibrous dysplasia of the clivus - A case study and literature review.

Fibrous dysplasia is a benign, congenital skeletal disorder which leads to the formation of fibro-osseous intramedullary bone lesions. Clival fibrous dysplasia is a rare variant which commonly presents asymptomatically with no findings on examination and is often picked up incidentally on radiological investigation. A 39-year-old female presented with a sudden onset headache of 3 days' duration alongside diplopia and right lower limb weakness upon examination. Computerized tomography head scan revealed an expansile clivus with a ground-glass appearance, magnetic resonance imaging brain scan revealed a predominantly hypointense signal on T1- and T2-weighted images and subsequent whole-body bone imaging confirmed the diagnosis of monostotic clival fibrous dysplasia. This case highlights the importance of considering monostotic clival fibrous dysplasia as a differential diagnosis in patients presenting with sudden onset symptoms of headache alongside cranial and peripheral nerve involvement, when other more sinister causes have been excluded.

Association of resistin (rs3745367) and urotensin II (rs228648 and rs2890565) gene polymorphisms with risk of type 2 diabetes mellitus in Indian population.

Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the same. Both Resistin, an adipose derived peptide hormone and Urotensin II a potent vasoconstrictor, are reported to be involved in the development of insulin resistance and T2DM but the results remain contradictory. Therefore, investigations were carried out to study the association of T2DM and single nucleotide polymorphism (SNP) in Resistin (RETN) gene at rs3745367 (+ 299 G > A) and Urotensin II (UTS2) gene at rs228648 (+ 143 G > A) and rs2890565 (+ 3836 C > T) in a North Indian population. Method: The present case-control study, conducted from August 2017 to July 2020, involved 168 T2DM patients and 102 healthy controls. SNPs rs3745367, rs228648 and rs2890565 were amplified from genomic DNA in the studied samples by polymerase chain reaction (PCR) using specific primers. The amplified products were genotyped by restriction fragment length polymorphism (RFLP) using particular restriction endonucleases. Clinical parameters viz. glycosylated haemoglobin (HbA1c), fasting blood glucose (FBG), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (CHL) and fasting insulin were determined by enzymatic methods. Result and conclusion: A statistically significant association between T2DM and RETN gene at SNP rs3745367 (p = 0.001) and UTS2 gene at SNP rs2890565 (p = 0.001) was observed. In RETN gene SNP rs3745367, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were found to be higher in GA + AA combined genotype than in GG genotype for T2DM subjects. Regression analysis revealed that SNP rs2890565 and HOMA-IR were independently associated with the risk of development of T2DM when three SNPs were taken as independent variable adjusted for clinical variables. Among four haplotypes, A/T was found associated with increased risk of T2DM as determined for rs228648 and rs2890565 of UTS2 gene. It can be concluded from these results that polymorphism at rs3745367 of RETN gene and at rs2890565 of UTS2 gene are associated with risk of T2DM in North Indian population.

SARS-CoV2 infectivity is potentially modulated by host redox status.

The current coronavirus disease (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) has emerged as a threat to global social and economic systems. Disparity in the infection of SARS-CoV2 among host population and species is an established fact without any clear explanation. To initiate infection, viral S-protein binds to the Angiotensin-Converting Enzyme 2 (ACE2) receptor of the host cell. Our analysis of retrieved amino acid sequences deposited in data bases shows that S-proteins and ACE2 are rich in cysteine (Cys) residues, many of which are conserved in various SARS-related coronaviruses and participate in intra-molecular disulfide bonds. High-resolution protein structures of S-proteins and ACE2 receptors highlighted the probability that two of these disulfide bonds are potentially redox-active, facilitating the primal interaction between the receptor and the spike protein. Presence of redox-active disulfides in the interacting parts of S-protein, ACE2, and a ferredoxin-like fold domain in ACE2, strongly indicate the role of redox in COVID-19 pathogenesis and severity. Resistant animals lack a redox-active disulfide (Cys133-Cys141) in ACE2 sequences, further strengthening the redox hypothesis for infectivity. ACE2 is a known regulator of oxidative stress. Augmentation of cellular oxidation with aging and illness is the most likely explanation of increased vulnerability of the elderly and persons with underlying health conditions to COVID-19.

Soil properties changes earthworm diversity indices in different agro-ecosystem.

BACKGROUND: Earthworm communities are generally very sensitive to physico-chemical properties of the soil in different agro-ecosystem i.e. cultivated or non-cultivated which directly or indirectly influence the earthworm survival. The difference in physico-chemical properties of soil at different sites contributed to the formation of population patches for earthworm species. Understanding the physico-chemical properties of soil at a particular site could facilitate the prediction of earthworm species at that site. The objective of the present study was to investigate the diversity, abundance, and distribution of earthworms in cultivated and non-cultivated agroecosystems and their physico-chemical properties affecting the earthworm diversity and abundance. RESULTS: Total 10 species of earthworms i.e. Amynthas alexandri, Amynthas morrisi, Eutyphoeus incommodus, Eutyphoeus waltoni, Metaphire birmanica, Metaphire houlleti, Metaphire posthuma, Octochaetona beatrix, Perionyx excavatus, and Polypheretima elongata, were reported. Out of all the reported species, Metaphire posthuma was found to be the most abundant earthworm species in both cultivated and non-cultivated agroecosystems with the occurrence at 56.81% sites. The Shannon-Wiener index (H), Margalef species richness index (DMg) and Pielou species evenness (E) was ranged from 0 to 0.86, 0 to 0.64 and 0.78 to 1 respectively. The principal component analysis resulted in four principal components i.e. PC1, PC2, PC3 and PC4 which contributing variance (%) of 22.96, 19.37, 14.23 and 10.10 respectively. The principal component analysis also showed that physico-chemical parameters of soil such as EC, pH, TDS, texture, OC, moisture, etc. play a critical role in earthworm distribution. CONCLUSION: The conventional farming system has a negative effect on the earthworm diversity in the soil while the physico-chemical properties of soil also have a determinant effect on the same. Earthworms abundance in the present study have significant direct relation with soil properties at a particular site and vice versa. The diversity indices also change due to the conventional farming system which directly affects the earthworm abundance.

Potential carcinogenic and non-carcinogenic health hazards of metal(loid)s in food grains.

Metal(loid) contamination of vital food grains such as wheat and rice is a very serious problem throughout the world because consumption of such contaminated food can lead to severe health effects in humans. Metal(loid) contamination of food crops can occur from different sources such as contaminated soil, irrigation water, and aerial deposition. Therefore, the present study was conducted to analyze potential non-carcinogenic and carcinogenic health impacts posed by different metal(loid)s (As Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, and Zn) via consumption of wheat and rice grown on metal(loid)-contaminated soils in areas around rivers (Beas and Sutlej) of Punjab, India. Among the metal(loid)s analyzed in wheat and rice samples, contents of As, Cd, Cr, Ni, and Pb were found to be above the international (FAO/WHO and EU) maximum permissible limits. The non-carcinogenic and carcinogenic health risk assessment of individual metal(loid)s revealed that As posed highest risk followed by Cd, Cu, Fe, Mn, and Pb. The values of indices calculated for analysis of combined non-carcinogenic, i.e., (hazard index; range 3.49-15.94) and carcinogenic (total carcinogenic risk index; range 8.30 × 10-4-131.62 × 10-4) risks for both crops were found to be many fold higher than the prescribed limits of 1.0 and 1.0 × 10-4, respectively. Thus, the analysis of combined risks posed by metal(loid)s indicated that human population consuming wheat and rice from the study area faced both non-carcinogenic and carcinogenic health risks. Therefore, immediate steps must be taken to reduce the levels of metal(loid)s in wheat and rice from the study area.

Regorafenib Prior to Selective Internal Radiation Therapy Using 90Y-Resin Microspheres for Refractory Metastatic Colorectal Cancer Liver Metastases: Analysis of Safety, Dosimetry, and Molecular Markers.

Background: This Phase II, open-label, study examined the safety of regorafenib followed by selective internal radiation therapy (SIRT) with regorafenib re-initiation in the treatment of metastatic colorectal cancer (mCRC) patients with liver metastases who are not surgical candidates. Methods: Patients received 160 mg regorafenib daily on a 21-day course followed by a 1 week washout prior to SIRT. Liver function was evaluated at 2 and 4 weeks after SIRT, and regorafenib re-initiated if liver function was normal. Patients were evaluated for safety, and restaged at weeks 6 and 12 following SIRT. In addition, protein and cytokine assays of blood were performed to identify candidate molecular biomarkers associated with outcomes. Individual patient voxel-based dosimetry assessment was performed post-SIRT. Results: Twenty-Five patients were enrolled and received a median 11 weeks regorafenib. Three patients received regorafenib, but not SIRT due to disease progression. The remaining 22 patients received SIRT with a median activity delivered to the liver of 38 mCi, mean normal liver dose of 14.98 Gy and tumor mean dose of 29.0 Gy with a tumor to normal ratio mean of 2.42. There were four treatment-related serious AEs and no treatment-related deaths. Median progression-free survival was 3.7 months and the median overall survival was 12.1 months. The relative densities of several biomolecules changed significantly during the course of treatment, most notably post-treatment increases in levels of sex-hormone binding globulin (SHBG) and decreased levels of the cytokine MIG (CXL9). Decreases in von Willebrand factor (VWF), the ankyrin repeat domain (ANKRD26), and MIG were associated with improved survival times. Post-treatment increases in alpha-2-macroglobulin (A2M) and the cytokine intercellular adhesion molecule (ICAM-1) were associated with reduced overall survival time, while increases in Eotaxin (CCL14) predicted longer overall survival times. Conclusions: The treatment of mCRC patients with liver metastases using regorafenib followed by SIRT was tolerable in this patient population. Further efficacy analysis of this treatment schema and analysis of potential molecular biomarkers using larger sample sizes is merited.

Prospect Theory Concepts Applied to Family Members of Nursing Home Residents with Cancer: A Good Ending Is a Gain.

Family members are often involved in medical decision-making on behalf of a nursing home resident. Prospect theory provides a framework for understanding how people weigh decisions. In the current study, prospect theory concepts are used to build understanding about how family members weigh medical decisions for an NH resident diagnosed with cancer. This is a secondary analysis of qualitative interview data from 24 family members of nursing home residents. Prospect theory concepts of gain, loss, risk, and reference point were used deductively in qualitative content analysis. Themes were developed by comparing content related to these four concepts, across the transcripts from the 24 participants. Three themes comprise the main findings, including "Don't prolong this," "A good ending is a gain," and "Experience can facilitate seeing the big picture." Prospect theory concepts applied to decisions faced by family members were useful in building an understanding of what participants considered as gains, losses, risks, and reference points. Many participants framed the medical decisions within the larger context of the resident's life and concluded that jeopardizing the chance for a peaceful dying process was too high a risk. Medical interventions were selected or avoided because of the impact on a comfortable dying process; considered a gain. Advance care planning discussions and goals of care discussions can benefit by directly addressing what residents/patients, families, and health practitioners consider outcomes worth pursuing and avoiding.

Desmoid type fibromatosis: A case report with an unusual etiology.

Desmoid type fibromatosis (DTF) is a rare, locally invasive, non-metastasizing soft tissue tumor. We report an interesting case of DTF involving the pancreatic head of a 54-year-old woman. She presented with intermittent dysphagia and significant weight loss within a 3-mo period. Laboratory findings showed mild elevation of transaminases, significant elevation of alkaline phosphatase and direct hyperbilirubinemia, indicating obstructive jaundice. Computerized tomography of the abdomen revealed a mass in the head of the pancreas, dilated common bile duct, and dilated pancreatic duct. Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound showed a large hypoechoic mass in the head of the pancreas causing extrahepatic biliary obstruction and pancreatic ductal dilation. The patient underwent a successful partial pancreatico-duodenectomy and cholecystectomy. She received no additional therapy after surgery, and liver function tests were normalized within nine days after surgery. Currently, surgical resection is the recommended first line treatment. The patient will be followed for any recurrence.

Orbital Morphometry: A Computed Tomography Analysis.

INTRODUCTION: The human orbit is a complex anatomic region, which plays predominant role in the evaluation of craniofacial complex. A thorough understanding of the relationship of the distance from orbital rim to the important vital structures of the orbital apex is required for the surgeon to perform safe and effective surgery. OBJECTIVES: To evaluate and compare the depth and distances from various points of the orbital rim to the fissures and foramina of the orbital apex between genders in the local population. METHODOLOGY: Linear measurements were conducted on 60 orbits from 30 patients who had undergone head computed tomography scan. These measurements were done utilizing the multiplanar reconstruction modes on computed tomography images with minimum slice thickness of 1 mm. RESULTS: Males have statistically significant larger orbits than females with higher mean measurements in all parameters, except for the distance from posterior ethmoidal foramen to the optic canal which was the same. However, there were no significant differences in all parameters between the right and left orbits. CONCLUSION: This study provides the absolute limit of safe internal orbital dissection in respect to the local population. Despite males having larger orbits than females, it is clinically negligible.

Depression and Anxiety following Coronary Artery Bypass Graft: Current Indian Scenario.

Epidemiological studies have shown a high prevalence of coronary artery disease among the Indian Population. Due to increasing availability and affordability of tertiary care in many parts of India, carefully selected patients undergo coronary artery bypass surgery to improve cardiac function. However, the procedure is commonly associated with depression and anxiety which can adversely affect overall prognosis. The objective of this review is to highlight early identifiable symptoms of depression and anxiety following coronary artery bypass graft (CABG) in Indian context so as to facilitate prompt intervention for better outcome. The current review was able to establish firm evidence in support of screening for depression and anxiety following CABG. Management of depression and anxiety following CABG is briefly reviewed.

Earthworms, pesticides and sustainable agriculture: a review.

The aim of this review is to generate awareness and understand the importance of earthworms in sustainable agriculture and effect of pesticides on their action. The natural resources are finite and highly prone to degradation by the misuse of land and mismanagement of soil. The world is in utter need of a healthy ecosystem that provides with fertile soil, clean water, food and other natural resources. Anthropogenic activities have led to an increased contamination of land. The intensification of industrial and agricultural practices chiefly the utilization of pesticides has in almost every way made our natural resources concave. Earthworms help in a number of tasks that support many ecosystem services that favor agrosystem sustainability but are degraded by exhaustive practices such as the use of pesticides. The present review assesses the response of earthworm toward the pesticides and also evaluates the relationship between earthworm activity and plant growth. We strictly need to refresh and rethink on the policies and norms devised by us on sustainable ecology. In an equivalent way, the natural resources should be utilized and further, essential ways for betterment of present and future livelihood should be sought.

Tuberculosis of the sternoclavicular joint.

PURPOSE: To review the diagnosis and treatment of tuberculosis of the sternoclavicular joint in 13 patients. METHODS: Records of 9 men and 4 women aged 26 to 47 (mean, 36.5) years who presented with tuberculosis of the right (n=8) or left (n=5) sternoclavicular joint were reviewed. RESULTS: All 13 patients had a raised erythrocyte sedimentation rate at presentation. Nine patients presented with systemic symptoms including malaise, fever, or loss of weight/appetite. Local symptoms included cold abscess (n=5), tenderness and non-fluctuant swelling (n=4), and discharging sinus (n=4). The mean duration of symptoms was 2.7 (range, 1-7) months. Four patients had multifocal involvement of the proximal ulna (n=1), lung (n=2), and meninges (n=1). Aspiration (n=3), fine needle aspiration cytology (n=4), drainage (n=2), or curettage (n=4) of the swelling, abscess, or sinus was performed, and the diagnosis was confirmed by histopathology (n=8), polymerase chain reaction (n=5), or culture (n=1). Two patients were diagnosed based on clinical suspicion. 11 patients responded to antituberculous therapy (ATT), and symptoms resolved after 6 to 8 weeks. Two patients did not respond to ATT after 3 months and were screened for immunocompromising disorders or drug resistance. Their CD4 count and CD4:CD8 ratio was low, and an immunomodulation regimen was prescribed as an adjunct to ATT. CONCLUSION: A high level of clinical suspicion is needed to diagnose tuberculosis of the sternoclavicular joint in patients with pain/tenderness, discharging sinus, or cold abscess. A combination of histopathological and microbiological tests, and PCR can confirm the diagnosis.

Assessment of esophageal involvement in systemic sclerosis and morphea (localized scleroderma) by clinical, endoscopic, manometric and pH metric features: a prospective comparative hospital based study.

BACKGROUND: Systemic sclerosis (SSc) is a generalized disorder of unknown etiology affecting the connective tissue of the body. It affects the skin and various internal organs. Gastrointestinal tract involvement is seen in almost 90% of the patients. Esophagus is the most frequently affected part of the gastrointestinal tract. Esophageal motility disturbance classically manifests as a reduced lower esophageal sphincter pressure (LESP) and loss of distal esophageal body peristalsis. Consequently, SSc patients may be complicated by erosive esophagitis and eventually by Barrett's esophagus and esophageal adenocarcinoma. Morphea, also known as localized scleroderma, is characterized by predominant skin involvement, with occasional involvement of subjacent muscles and usually sparing the internal organs. The involvement of esophagus in morphea has been studied very scarcely. The proposed study will investigate the esophageal involvement in the two forms of scleroderma (systemic and localized), compare the same and address any need of upper gastrointestinal evaluation in morphea (localized scleroderma) patients. METHODS: 56 and 31 newly and already diagnosed cases of SSc and morphea respectively were taken up for the study. All the patients were inquired about the dyspeptic symptoms (heartburn and/or acid regurgitation and/or dysphagia). Upper gastrointestinal endoscopy, esophageal manometry and 24-hour pH monitoring were done in 52, 47 and 41 patients of SSc; and 28, 25 and 20 patients of morphea respectively. RESULTS: Esophageal symptoms were present in 39 cases (69.6%) of SSc which were mild in 22 (39.3%), moderate in 14 (25%), severe in three (5.3%); while only four cases (7.1%) of morphea had esophageal symptoms all of which were mild in severity. Reflux esophagitis was seen in 17 cases (32.7%) of SSc and only two cases (7.14%) of morphea. Manometric abnormalities were seen in 32 cases (68.1%) of SSc and none in morphea. Ambulatory 24-hour esophageal pH monitoring documented abnormal reflux in 33 cases (80.5%) of SSc and no such abnormality in morphea. CONCLUSION: While the esophageal involvement is frequent in SSc, no such motility disorder is seen in morphea. Meticulous upper gastrointestinal tract evaluation is justified only in SSc and not in morphea.

Explicit role of peroxisome proliferator-activated receptor gamma in gallic acid-mediated protection against ischemia-reperfusion-induced acute kidney injury in rats.

BACKGROUND: Gallic acid is a polyphenolic compound and is reported to be renoprotective because of its antioxidant activity in various preclinical studies. Gallic acid has been reported to activate peroxisome proliferator-activated receptor gamma (PPAR-γ) in vitro. However, the relevance of the interplay between gallic acid and PPAR-γ in various pathologic conditions is yet to be established in vivo. The present study investigated the protective role of gallic acid against ischemia-reperfusion-induced acute kidney injury (AKI) and the possible involvement of PPAR-γ in gallic acid-mediated renoprotection. MATERIALS AND METHODS: The AKI was induced in rats through bilateral clamping of renal arteries for 40 min followed by reperfusion for 24 h. The AKI was assessed by the quantification of creatinine clearance, blood urea nitrogen, uric acid, potassium level, fractional excretion of sodium, and urinary microproteins. The oxidative stress in renal tissues was quantified in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. The histopathologic changes in renal tissues were assessed by hemotoxylin and eosin staining. The rats were administered gallic acid (50, 100, and 200 mg/kg) orally for 7 d before subjecting them to AKI. RESULTS: The renal ischemia-reperfusion induced significant changes in plasma, urinary, and tissue parameters. The administration of gallic acid at three dose levels offered a significant protection against renal ischemia-reperfusion-induced AKI. The prior treatment with PPAR-γ antagonist, bisphenol A diglycidyl ether, significantly abolished the renoprotective effect of gallic acid that confirms the involvement of PPAR-γ in gallic acid-mediated renoprotection. CONCLUSIONS: It is concluded that the activation of PPAR-γ significantly contributes toward gallic acid-mediated protection against ischemia-reperfusion-induced AKI.