Preparation and physicochemical characterization of whitlockite/PVA/Gelatin composite for bone tissue regeneration.

This work used a straightforward solvent casting approach to synthesize bone whitlockite (WH) based PVA/Gelatin composites. WH nanoparticles (NPs) were synthesized using the wet precipitation method, followed by their addition into the PVA/Gelatin matrix at concentrations from 1% to 10%. The physicochemical characterization of the prepared PVA/Gelatin/WH composite was carried out using ATR-FTIR, Optical profilometry, a Goniometer, a Universal tensile testing machine (UTM), and scanning electron microscopy (SEM) techniques. The ATR-FTIR analysis confirmed the formation of noncovalent interactions between polymeric chains and WH NPs and the incorporation of WH NPs into the polymer cavities. SEM analysis demonstrated increased surface roughness with the addition of WH NPs, supporting the results obtained through optical profilometry analysis. The mechanical properties of the prepared composite showed an increase in the tensile strength with the addition of WH filler up to 7% loading. The prepared composite has demonstrated an excellent swelling ability and surface wettability. The reported results demonstrate the exceptional potential of the prepared composite for bone tissue regeneration.

Retrospective Diagnosis of Ca Thyroid on Thyroid Pertechnetate Scan -A part of Routine Post Thyroidectomy Work up For Nontoxic Multi Nodular Goiter.

Unsuspected thyroid cancer can be detected in multinodular goiter (MNG) where the risk of malignancy is 7-9%. Fine needle aspiration (FNAc) is performed in case of suspicious findings on ultrasound. With benign FNAC results there is no need for surgery unless the patient has pressure symptoms or cosmetic concerns, but the risk of overlooked malignancy is always present. We present the case of a patient with unexpected detection of papillary thyroid cancer on thyroid scan.

Comparison Between Early Appendectomy vs. Conservative Management in Cases of Appendicular Mass.

INTRODUCTION: At present, the treatment of choice for appendicular masses is unclear. Recent studies claimed that conservative management of appendicular masses was safe in terms of frequency of perforation. However, there is controversy in the existing literature. OBJECTIVE: This research is designed to compare the results of early appendectomy versus conservative management of appendicular masses. MATERIAL AND METHODS: It was a randomized controlled trial performed in the Combined Military Hospital, Lahore. The study lasted six months, from 01/03/2019 to 30/09/2019. It involved 60 patients of both genders aged between 16 and 70 years diagnosed with appendicular masses with an Alvarado score of 4-7. These patients were randomly divided into two treatment groups. In Group A patients, an early appendectomy was performed, while patients in Group B were managed conservatively. Outcome variables were the mean length of hospital stay and frequency of appendicular perforation. RESULTS: The mean age of the patients was 26.8±11.9 years. There were 33 (55.0%) male and 27 (45.0%) female patients, with a male-to-female ratio of 1.2:1. The mean length of hospital stay was significantly longer in patients managed conservatively as compared to those undergoing early appendectomy (2.80±1.54 vs. 1.83±0.83; p=0.004). However, the frequency of perforation was not significantly higher in the conservative group as compared to the early appendectomy group (16.7% vs. 10.0%; p=0.448). CONCLUSION: Conservative management of patients with appendicular mass was associated with prolonged hospital stays, yet it was found equally safe in terms of frequency of appendicular perforation, which advocates conservative management of patients with appendicular mass, particularly in high-risk patients.

Graphene Based Nanohybrid Aptasensors in Environmental Monitoring: Concepts, Design and Future Outlook.

In view of ever-increasing environmental pollution, there is an immediate requirement to promote cheap, multiplexed, sensitive and fast biosensing systems to monitor these pollutants or contaminants. Aptamers have shown numerous advantages in being used as molecular recognition elements in various biosensing devices. Graphene and graphene-based materials/nanohybrids combined with several detection methods exhibit great potential owing to their exceptional optical, electronic and physicochemical properties which can be employed extensively to monitor environmental contaminants. For environmental monitoring applications, aptamers have been successfully combined with graphene-based nanohybrids to produce a wide range of innovative methodologies. Aptamers are immobilized at the surface of graphene based nanohybrids via covalent and non-covalent strategies. This review highlights the design, working principle, recent developmental advances and applications of graphene based nanohybrid aptasensors (GNH-Apts) (since January 2014 to September 2021) with a special emphasis on two major signal-transduction methods, i.e., optical and electrochemical for the monitoring of pesticides, heavy metals, bacteria, antibiotics, and organic compounds from different environmental samples (e.g., water, soil and related). Lastly, the challenges confronted by scientists and the possible future outlook have also been addressed. It is expected that high-performance graphene-based nanohybrid aptasensors would find broad applications in the field of environmental monitoring.

Extraosseous soft tissue uptake-in Multiple Myeloma.

Tc-99m Methylene Diphosphonate (MDP) bone scintigraphy has been used for the assessment of benign as well as malignant skeletal conditions. Non-osseous radiotracer uptake on bone scan is an unusual finding. It is usually performed for metastatic bone disease, and is generally not an indication in multiple myeloma, as osteolytic lesions typically show no radiotracer uptake. Despite this, substantial number of multiple myeloma patients undergo bone scintigraphy due to their presentation imitating a metastatic bone disease. We describe a case of multiple myeloma, where extra osseous uptake in lung and diffuse hepatic, has been noted on bone scan.

Synthesis, Characterization and Process Optimization of Bone Whitlockite.

Whitlockite, being the second most abundant bio-mineral in living bone, finds huge applications in tissue regeneration and implants and its synthesis into its pure form has remained a challenge. Although precipitation of whitlockite phase has been reported recently in many publications, effects of various parameters to control such phase as well as conditions for the bulk preparation of this extremely important bio-mineral have not been investigated so far. In this work, we report the precipitation of pure whitlockite phase using common precursors. As reported in the literature, whitlockite is stable in a narrow pH range, therefore; optimization of pH for the stabilization of whitlockite phase has been investigated. Additionally, in order to narrow down the optimum conditions for the whitlockite precipitation, effect of temperature and heating conditions has also been studied. The obtained solids were characterized using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). From PXRD analysis, it was observed that heating the precursor's mixture at 100 °C with subsequent aging at the optimized pH resulted in the precipitation of pure whitlockite phase. These results were further confirmed by TGA, SEM and Raman spectroscopy analysis and it was confirmed that the conditions reported here favor whitlockite precipitation without formation of any secondary phase. These reaction conditions were further confirmed by changing all the parameters like aging, heating time, feed rate of precursors one by one. From PXRD analysis of these samples, it was concluded that not only pH but temperature, heating time, aging time and feed rate effect simultaneously on the precipitation of pure whitlockite phase and a subtle change in any of these parameters could lead to the formation of undesired stable secondary calcium phosphate phases.

Malignant Melanoma of the Female Genital Tract: Experience of an Oncology Center in Pakistan.

Introduction Malignant melanoma, which arises from melanocytes or pigment cells, is one of the most common forms of epithelial cancer. Cutaneous and noncutaneous melanomas differ clinically and genetically. Mucosal melanomas are rare. In the female genital tract, the most frequent location of melanoma is the vulva, whereas the vagina is seldom affected. The occult nature of their anatomical location contributes to the late presentation and late diagnosis of vaginal melanoma, resulting in an exceedingly poor patient prognosis. The present study describes the incidence, symptoms, management, and prognosis of women in Pakistan with malignant melanoma of the vulva, vagina, and cervix. Materials and methods The Hospital Information System of Shaukat Khanam Memorial Cancer Hospital and Research Center was searched electronically to identify patients diagnosed with malignant melanoma from January 1995 to December 2017. Patients with cutaneous malignant melanoma, multiple primary tumors, and metastases to the female genital tract from primary tumors located elsewhere were excluded. All included patients had been diagnosed with primary malignant melanoma of the female genital tract. Results The search of medical records identified 271 patients with malignant melanoma, of whom 13 had primary malignant melanomas of the female genital tract. Of these 13 patients, nine, three, and one had primary vaginal, vulvar, and cervical melanomas, respectively. Median age at presentation was 60 years (range, 30-70 years), with 10 patients being post-menopausal. The most common presentations were per-vaginal bleeding and per-vaginal discharge (five patients each). The mean duration of symptoms was 7.46 months. Seven patients underwent wide local excision. Six patients had nodular type malignant melanoma, two had superficial spreading type, and five were unclassified. Nine patients had pathological T4 disease, and two had pathological T3. Mean Breslow depth was 5.4 millimeters (mm), with 10 patients having tumor depth >4 mm. Eight patients were positive for the microscopic involvement of margins. The mean time to recurrence was 11.8 months (range, 1-24 months), and the mean time to metastasis was 17.6 months (range, 2-44 months). The median survival after surgery was 25 months (range, 2-75 months). Conclusion This study is the first to report the incidence, symptoms, management, and prognosis of patients in Pakistan with malignant melanoma of the female genital tract. Meta-analyses and prospective multicenter studies are needed.

Prognostic Factors for Recurrence in Esophageal Cancer Patients Treated With Neoadjuvant Therapy and Surgery: A Single-institution Analysis.

Background The purpose of this study is to analyze potential predisposing factors for a higher risk of recurrence in our esophageal cancer patients managed with neoadjuvant chemotherapy, radiation therapy, and surgery, and to determine their impact on disease-free survival (DFS) and time to recurrence. Methods A total of 154 of 232 patients staged T1b to T4a managed electively at our institute from July 2005 through July 2015 with a tri-modality approach were retrospectively evaluated. Basic demographic, clinical, radiological, operative, and pathological disease-related parameters, along with waiting time for surgery and type of neoadjuvant modality used, were assessed as potential risk factors. The primary endpoint was the impact of these on the risk of recurrence. The secondary endpoint was to study their relation on DFS and time to recurrence. Results The recurrence rate in this particular study was 33.1% over a median follow-up of 35 months (interquartile range = 19-50.3). The median time to recurrence was 12 months, and 94% of recurrences occurred within two years. The median DFS was 33 months, and the one- and three-year DFS was 90% and 72%, respectively. On univariate and multivariate analysis, a complete pathological response (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.41-10.11), negative resection margins (HR: 5.9, 95% CI: 1.69-20.45), and a low nodal index (HR: 6.3, 95% CI: 1.37-28.67 for an index of 0.1-0.2; and HR: 15.2, 95% CI: 0.96-241.73 for an index of >0.2) were found as statistically significant (P = < 0.05) for risk to recurrence. In addition to these three, a low comorbidity index (P = 0.03; HR: 3.5; 95% CI: 1.16-10.52) was an individual positive predictor of DFS. Conclusions A complete pathological response, low nodal index, and margin-negative resection were the identified predictors of freedom from recurrence, with a better DFS and a low comorbidity index as additional indicators of prolonged DFS.

Progress in cancer biomarkers monitoring strategies using graphene modified support materials.

Cancer is the one of the fatal and dreaded disease responsible for huge number of morbidity and mortality across the globe. It is expected that the global burden will increase to 21.7 million fresh cancer cases as compared to present estimate of 18.1 million cancer cases in addition to nearly 9.6 million cancer deaths worldwide. In response to cancerous or certain benign conditions; specific type of tumor or cancer markers (biomarkers) are produced at much higher levels which are secreted into the urine, blood, stool, tumor or other tissues. Therefore, the efficient and early detection of cancer biomarkers is necessary which can offer a reliable way for cancer patient screening and diagnosis. This process not only helps in the evaluation of pathogenic processes but also the prognosis of different cancers and pharmacological responses to therapeutic interventions are secured. Over the past several years, electrochemical detection methods have proved to be the most attractive methods among many, due to the advantages, such as simple instrumentation, portability, low cost and high sensitivity. Furthermore, the modifications of these electrochemical immunosensors by utilizing various types of nanomaterials enable these systems to detect trace amount of target tumor markers. Hence, herein, we intend to review the selective works on electrochemical detection of various biomarkers using wide range of nanomaterials with a particular focus on graphene.

Risk factors and patterns of recurrence after curative resection in Gastroesophageal Junction Adenocarcinoma.

OBJECTIVES: We looked at risk factors and patterns of recurrence following surgical treatment of Gastro-Oesophageal Junction carcinoma (GOJC). METHODS: Electronic medical records of patients with GOJC undergoing resection with curative intent between Jan 2009 and June 2017 at Shaukat Khanum Memorial Cancer Hospital were reviewed. GOJ cancer was classified as per Siewert classification. Clinical and operative details were studied and data was analysed using SPSS 20. RESULTS: During the study period, we identified 78 patients with GOJ adenocarcinoma (38 patients with GOJ Type-I, 16 with Type-II tumors and 24 patients with GOJ Type-III tumors). Median age was 56 years ± 1.1. Male to female distribution was 72 versus 28%. Carbo-Pacli /5-FU based XRT verses Magic protocol (p<0.015) and advanced pathological T.-stage (p-value<0.032) were found to be statistically significant risk factors for recurrence. After a median follow up of 17.8 months+/- 1.5, 20 patients developed recurrence of which five had local recurrence, three had regional recurrence, eight had distant metastases and four had both local and distant metastases. CONCLUSION: The incidence of recurrence following curative resection of GOJC is 25%. Type of neoadjuvant treatment, waiting time for surgery and advanced T-stage are a risk factor for recurrence.

Management of parathyroid adenoma: An institutional review.

To assess indications, role of preoperative localization, intra-operative details and post operative recovery of patients who underwent parathyroidectomy. Data of adult patients diagnosed with parathyroid adenoma with primary hyperparathyroidism from January 2006 to September 2016 was retrieved from medical records. Demographics, preoperative investigations, operative details and follow up were studied. Seventeen patients diagnosed with primary hyperparathyroidism (PHPT) due to parathyroid adenoma, were managed by parathyroidectomy by skin collar incision. Median age was 46 (IQR 35 - 57). Median duration of surgery was 80min (IQR of 15-120 min) and median blood loss was 15ml. Thyroid nodules were observed in three patients, which were managed by thyroid lobectomy. Preoperative Sestamibi scan localized adenoma in 14 patients (frequency 82%). Intraoperative methylene blue and endoscopic ultrasound were not used. Parathormone (PTH) and calcium level were decreased in all post operative patients except one and no recurrence was seen on follow up. Parathyroid adenomas can be successfully localized with a pre-operative Sestamibi scan. Surgery remains the mainstay of treatment.

Risk Factors For Chyle Leak After Esophagectomy.

BACKGROUND: Chylothorax is an uncommon (3-8% risk) but potentially fatal complication of esophagectomy with poorly understood risk factors. It has a high morbidity due to loss of fluids, electrolytes, and other nutrients, loss of lymphocytes and immune dysfunction. METHODS: Retrospective chart review of adult patients who underwent esophagectomy between 2009 and 2016 was performed. Cases with chyle leak were identified according to a set criteria. Clinical features, operative findings and postoperative variables were recorded and predictors of chyle leak were analyzed. RESULTS: During the study period, a total of 193 adult patients underwent esophagectomy of which 186 received neo adjuvant chemotherapy. The mean age was 53 years with 118 males and 74 females. Type of procedure performed was 3-stage esophagectomy in 98, Transhiatal esophagectomy in 79 and Ivor-Lewis esophagectomy in 15 patients. Chyle leak was identified in 9 (4.6%) patients. There was no significant association of chyle leak with age, gender, co-morbid, level of tumor, Neoadjuvant therapy and Type of esophagectomy. Chest drain output on postoperative day 5 was significantly predictive of chyle leak (p-value<0.05). Drain output more than 1000 on day 4 was highly suggestive of chyle leak (p-value<0.05). Day on which chest drain was removed was also found to be significantly related to chyle leak (p-value <0.05). CONCLUSIONS: No significant preoperative risk factors were identified for chyle leak. High chest drain output on postoperative day 5 and drain output more than 1000 on day 4 are significant predictors of chyle leak.

Vascular Resection and Reconstruction in Pancreatic Tumours.

Option for borderline resectable pancreatic cancer is pancreaticoduodenectomy (PD) with vascular resection and reconstruction. We would like to share our experience of vascular reconstruction. First patient was a 51-year male with pancreatic head carcinoma, involving posterior wall of portal vein (PV) and replacing right hepatic artery (RHA). Along with PD, he underwent PV and RHA resection and reconstruction. Second case was a 33-year female who had distal pancreatic cyst and PV-splenic vein junction involved by tumor. Distal pancreatectomy+splenectomy and PV primary resection-reconstruction was done. Third case was a 72-year male with pancreatic neck adenocarcinoma involving PV-SMV junction. Subtotal pancreatecomy+splenectomy was done along with PV-reconstruction via splenic vein patch graft. Fourth case was a 77-year male with cystic pancreatic head mass involving PV. PD with resection and reconstruction of portal vein was done. Fifth case was a 35-year female with peri-ampullary tumor replacing RHA, coursing through the pancreatic parenchyma. So RHA was resected and reconstructed in an end-to-end fashion. Vascular resection-reconstruction can be done in borderline pancreatic cancer patients, and a considerable survival benefit can be achieved.

Symmetrical aryl linked bis-iminothiazolidinones as new chemical entities for the inhibition of monoamine oxidases: Synthesis, in vitro biological evaluation and molecular modelling analysis.

The multifactorial nature of Parkinson's disease necessitates the development of new chemical entities with inherent ability to address key pathogenic processes. To this end, two series of new symmetrical 1,2- and 1,4-bis(2-aroyl/alkoylimino-5-(2-methoxy-2-oxoethylidene)-4-oxo-thiazolidin-3-yl)benzene derivatives (3a-g and 5a-e) were synthesized in good yields by the cyclization of 1,2- and 1,4-bis(N'-substituted thioureido)benzene intermediates with dimethyl acetylenedicarboxylate (DMAD) in methanol at ambient temperature. The bis-iminothiazolidinone compounds were investigated in vitro for their inhibition of monoamine oxidase (MAO-A & MAO-B) enzymes with the aim to identify new and distinct pharmacophores for the treatment of neurodegenerative disorders like Parkinson's disease. Most of the designed compounds exhibited good inhibitory efficacy against monoamine oxidases. Compound 5a was identified as the most potent inhibitor of MAO-A depicting an IC50 value of 0.001µM, a 4-fold stronger inhibitory strength compared to standard inhibitor (clorgyline: IC50=0.0045µM). Molecular docking studies provided insights into enzyme-inhibitor interactions and a rationale for the observed inhibition towards monoamine oxidases.

Quinazolines and quinazolinones as ubiquitous structural fragments in medicinal chemistry: An update on the development of synthetic methods and pharmacological diversification.

Nitrogen-rich heterocycles, particularly quinazolines and quinazolinones, represent a unique class of diversified frameworks displaying a broad spectrum of biological functions. Over the past several years, intensive medicinal chemistry efforts have generated numerous structurally functionalized quinazoline and quinazolinone derivatives. Interest in expanding the biological effects, demonstrated by these motifs, is growing exponentially, as indicated by the large number of publications reporting the easy accessibility of these skeletons in addition to the diverse nature of synthetic as well as biological applications. Therefore, the main focus of the present review is to provide an ample but condensed overview on various synthetic approaches providing access to quinazoline and quinazolinone compounds with multifaceted biological activities. Furthermore, mechanistic insights, synthetic utilization, structure-activity relationships and molecular modeling inputs for the potent derivatives have also been discussed.