Role of sacituzumab govitecan in solid tumors.

OBJECTIVE: To evaluate the antibody-drug conjugate- sacituzumab govitecan, its pharmacological properties, toxicity, data supporting efficacy against a wide variety of solid tumors beyond breast cancer, and potential future uses. DATA SOURCES: Articles in MEDLINE/PubMed databases and the National Institutes of Health Clinical Trials Registry (http://www. clinicaltrials.gov) between January 1, 2015, and July 1, 2021 using MeSH terms sacituzumab govitecan(- hziy) and solid tumors were reviewed. DATA SUMMARY: Antibody-drug conjugates (ADC's) are a subclass of emerging cancer therapeutics which combines chemotherapy with targeted antibodies. Sacituzumab govitecan (SG) is a novel antibody drug conjugate that has recently been approved by the Food and Drug Administration (FDA) in adult patients for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. The approval of sacituzumab govitecan provides a new option for solid tumors that need to be further explored. In this review article, we discussed the pharmacokinetics, pharmacodynamics, safety profile of sacituzumab govitecan and various ongoing clinical trials on sacituzumab govitecan. CONCLUSION: Sacituzumab is a significant advancement made in cancer therapy. SG has showed significantly improved Health-related quality of life (HRQoL) in addition to prolonged progression free survival and Over all survival in addition to maintaining a good safety profile. Multiple clinical trials on SG are ongoing to evaluate the potential use of SG as neoadjuvant therapy in triple negative breast cancer, as an Adjuvant therapy, in combination with immunotherapy, and also for various solid tumors.

First report of post-harvest Fusarium rot of mandarin Citrus reticulata cv. 'Kinnow' caused by Fusarium equiseti in Pakistan.

Citrus reticulata cv. 'Kinnow' mandarin is the most popular and widely grown fruit crop in Pakistan. During 2017, a survey was conducted to the local citrus fruit markets of Faisalabad, Pakistan. Citrus fruits (n=50) exhibiting stem end rot and fruit rot were collected with 15% disease incidence. The stem end region showed light to dark brown lesions and white fungal growth was also observed in the severely infected fruit. Infected fruit were excised into 2mm2 segments, surface disinfected with 1% NaClO, rinsed with sterilized water and dried. Later, these tissues were placed on potato dextrose agar (PDA) medium and subsequently incubated at 25 °C. Purified isolates produced white colonies with beige pigmentation. The frequency of fungal isolation was 47%. Microscopic observations revealed that macroconidia (n=50) had 5 to 6 septations, with a prominent dorsiventral curvature, tapered and elongated apical cell, and a foot shape basal cell. The macroconidia were measuring 22 to 45 × 2.9 to 4.3 µm with an average of 31 × 3.6 µm. However, microconidia were not observed. Chlamydospores were globose, intercalary, solitary, or in pairs, appearing in chains (Leslie and Summerell 2006). For molecular identification, DNA was extracted from all isolates. The internal transcribed spacer region (ITS) ITS1/4 (White et al. 1990), translation elongation factor-1 alpha (TEF) EF1/2 (O'Donnell et al. 1998), and RNA polymerase II subunit 1 (RPB1) (O'Donnell et al. 2013) were amplified using PCR and the product was subsequently sequenced. Based on BLAST analysis, the isolate was identified as Fusarium equiseti (FUS-21). The sequences of the representative isolate FUS-21 were deposited in the GenBank with accession numbers (ITS, MH581300), (TEF, MK203749), and (RPB1, MW596599) showing more than 99% similarity with ITS accession GQ505683, TEF accession GQ505594, and 100% to RPB1 accession JX171481. To determine the pathogenicity, 40 healthy surface disinfested citrus fruit were taken. The fruit were inoculated by creating artificial wounds on the surface with a sterilized needle and 10 µL of 105 spores/mL was deposited in the wounds. In case of control fruit were inoculated with 10 µL sterilized distilled water only, and incubated at 25 °C. All fruit inoculated with the putative pathogen, developed symptoms like the original fruit from which they were isolated. The pathogenicity test was repeated twice. Visible white mycelium appeared at the stem end region and the fruits became dried as the infection progressed. However, the control fruit remained asymptomatic. The pathogen was re-isolated from infected fruit and identified based on morphometric and molecular analysis. Previously we have reported F. oxysporum causing citrus fruit rot in Pakistan (Moosa et al. 2020). This is the first report of F. equiseti causing post-harvest rot of citrus fruits in Pakistan. Kinnow is an important fruit crop of Pakistan with huge export value the management of Fusarium rot is quite important to save the loss of fresh produce.

First report of brown leaf spot of rice caused by Bipolaris zeicola in Pakistan.

Rice (Oryza sativa L.) is one of the highly consumed cereal grain crops in Pakistan. In September 2017, leaf samples of cultivar Basmati-385 showing brown to dark brown spots (5 to 9 mm in diameter) that were oval or cylindrical in shape with a chlorotic yellow halo and grayish tan centers were collected from fields near the University of Agriculture, Faisalabad (31.43633 N 73.05981 E). Average disease incidence was 69% in six rice fields that were sampled for diseased plants with visible symptoms. To isolate the pathogen, from 20 diseased leaves, 5 mm2 segments from the margins of lesions were cut, rinsed with sterile distilled water (SDW), surface disinfected by 70% ethanol and again rinsed with SDW. The samples were dried on sterilized filter paper discs, plated on potato dextrose agar (PDA) and incubated at 27°C for 5 to 7 days. Twelve isolates were sub-cultured and single-sporing was performed to obtain pure cultures. Fungal isolates with light to dark gray in color, thick or fluffy aerial mycelium, circular and smooth margins were obtained after 7 days of incubation. Conidia were 47-83 µm × 10-17 µm (n=100), with 4 to 10 distosepta, dark or olivaceous brown, straight or moderately curved, and the cells at the ends occasionally looked paler than those in the middle. Conidiophore of the fungus were simple, smooth, cylindrical, septate, and straight to flexuous. These characteristics resembled those of Bipolaris zeicola (Stout) Shoemaker (Manamgoda et al. 2014). For molecular identification, genomic DNA (isolate SU-11) was extracted and the internal transcribed spacer (ITS) region, large subunit (LSU) of ribosomal DNA, translation elongation factor (tef), glyceraldehyde 3-phosphate dehydrogenase (gpd), and RNA polymerase II second largest subunit (rpb2) genes were amplified and sequenced by using the primers ITS1-F/ITS4-R (White et al. 1990), LROR-F/LR5-R (Schoch et al. 2012), EF1-983F/EF1-2218R (Rehner and Buckley 2005), GPD1F/GPD2R (Berbee et al. 1999), and 5F2/7CR (O'Donnell et al. 2007), respectively. BLASTn searches showed 100% homology with the LSU and rpb2 sequences of B. zeicola (GenBank Accession Nos. MH876201 and HF934842) and 98-99% similarity with ITS, tef, and gpd sequences of B. zeicola (GenBank Accession Nos. KM230398, KM093752 and KM034815). The sequences of ITS, LSU, tef, gpd, and rpb2 were deposited in GenBank with accession numbers MN871712, MN877767, MN867685, MN904511 and MT349837, respectively. To fulfill Koch's postulates, 25 greenhouse-grown rice plants (cv. Basmati-385) at 2- to 3-leaf stage were spray inoculated with a spore suspension (105 spores/ml; isolate SU-11) prepared in SDW. Plants were covered with plastic wraps to maintain humid conditions for 24 hours and incubated at 27°C for one week. Similarly, ten non-inoculated plants sprayed with SDW served as controls. After one week, observed symptoms were similar to those from natural infections and no disease symptoms were observed on the non-inoculated plants. The experiment was repeated twice and the pathogen was re-isolated from the infected leaves and characterized morphologically. Globally, B. zeicola has also been reported to cause the leaf spot of rice and maize plants (Sivanesan 1987; Kang et al. 2018). To our information, this is the first report of B. zeicola causing brown leaf spot of rice in Pakistan. The increasing risk of this fungal pathogen in the rice-growing areas of Pakistan need a rigorous exploration and outreach effort to develop effective management practices.

PARP inhibitors.

Poly (ADP-ribose) polymerases, abbreviated as PARPs, are a group of familiar proteins that play a central role in DNA repair employing the base excision repair (BER) pathway. There about 17 proteins in this family out of which the primary nuclear PARPs are PARP-1, PARP-2, PARP-3, and tankyrases 1 and 2 (PARP-5a and -5b) .The PARP family members are known to engage in a wide range of cellular activities, for example, DNA repair, transcription, cellular signaling, cell cycle regulation and mitosis amongst others. The chief functional units of PARP-1 are an amino terminal DNA binding domain (DBD), a central auto modification domain (AMD), and a carboxyl-terminal catalytic domain (CD). PARP inhibitors are currently undergoing clinical trials as targeted treatment modalities of breast, uterine, colorectal and ovarian cancer. This review summarizes current insights into the mechanism of action of PARP inhibitors, its recent clinical trials, and potential next steps in the evaluation of this promising class of anti-cancer drugs.

Carcinogenesis of PIK3CA.

PIK3CA is the most frequently mutated oncogene in human cancers. PIK3CA is phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha. It controls cell growth, proliferation, motility, survival, differentiation and intracellular trafficking. In most of human cancer alteration occurred frequently in the alpha isoform of phosphatidylinositol 3 kinase. PIK3CA mutations were most frequent in endometrial, ovarian, colorectal, breast, cervical, squamous cell cancer of the head and neck, chondroma, thyroid carcinoma and in cancer family syndrome. Inhibition of PI3K signaling can diminish cell proliferation, and in some circumstances, promote cell death. Consequently, components of this pathway present attractive targets for cancer therapeutics. A number of PI3K pathway inhibitors have been developed and used. PI3K inhibitors (both pan-PI3K and isoform-specific PI3K inhibitors), dual PI3K-mTOR inhibitors that are catalytic site inhibitors of the p110 isoforms and mTOR (the kinase component of both mTORC1 and mTORC2), mTOR catalytic site inhibitors, and AKT inhibitors are the most advanced in the clinic. They are approved for the treatment of several carcinomas.

Association of socioeconomic classes with diet, stress and hypertension.

OBJECTIVE: To evaluate the relationship between diet and socioeconomic conditions and find out the prevalence of stress and Hypertension in different socioeconomic classes. METHODS: A cross-sectional study was conducted from May 2010 to October 2011, 176 people from four different socio economic Strata (low class, low middle class, upper middle class, and high class) were selected, which were defined on the basis of monthly income. Complete dietary intake was assessed with the last 3 days' dietary record, dietary patterns and restrictions. Background information and Stress level were evaluated by a preformed questionnaire and blood pressure was taken with the aneroid manometer. RESULT: A total of 176 people were interviewed for diet, blood pressure and stress was measured. The High socioeconomic Stratum was found to have the highest number of people having hypertension 15 (27.8%), taking medications 21 (38.9%), 18 (33.3%) multi vitamin supplements, and with an overall lower calorie intake 1617.31 +/- 698.99 as compared to other strata. It also had the highest number of people who thought they were active 44 (81.5%). The High middle Socioeconomic Stratum was similar with the High class, in having the most hypertensive people 10 (27.8%) and they had least chance of developing stress related health illnesses 6 (16.7%). Individuals living below poverty line had the highest prevalence ratio of stress 16 (36.4%) and they were considered as least physically active 30 (68.2%). CONCLUSION: Highest frequency of Hypertension was in high class and high middle income group. The low class had the highest ratio of stress. There was a difference in type of food, but not much in calorie intake.

Environmental Risks of Microplastics on the Spatial and Temporal Gradient in a River Originating from the Western Himalayas.

The presence of microplastics in different environmental matrices has raised many concerns about potential effects of microplastics on humans and freshwater ecosystems. In Pakistan, rivers potentially receive microplastics from anthropogenic activities in their catchments. However, research studies regarding microplastics' presence, distribution, and risks are scarce in Pakistan. To bridge the gap, the present study was conducted to evaluate microplastic pollution in the Chenab River. Surface water samples were collected from selected sites on the Chenab River using a manta trawl in the low-flow season during postmonsoon (October) 2019 and 2020 and in the high-flow season during monsoon (July) 2020 and 2021. Samples were digested, followed by density separation and filtration. Identification and polymer characterization of microplastics were completed using stereomicroscopy and attenuated total reflection Fourier transform infrared spectroscopy, respectively. Microplastics were found in all samples with significant spatiotemporal variation in microplastic concentration, with an average of 45.98 ± 10.45 microplastics/m3 in the low-flow season and 34.66 ± 16.15 microplastics/m3 in the high-flow season. Among microplastic shapes, fibers were the most dominant shape, whereas polyethylene terephthalate (38.2%) and polypropylene (19%) were the most abundant polymers. Polymer risk index analysis and pollution load index demonstrated that most of the sites ranked as safe. The potential ecological risks from single polymers and combined polymers showed minor risks posed by microplastics. The present study is the first step to focus on microplastic pollution in the Chenab River; it will help river managers to mitigate the microplastic pollution without compromising the ecological integrity of the river. Environ Toxicol Chem 2023;42:727-739. © 2023 SETAC.

Morpho-physiological and biochemical response of wheat to various treatments of silicon nano-particles under drought stress conditions.

Silicon nanoparticles (Si-NPs) have shown their potential for use in farming under water-deficient conditions. Thus, the experiment was accomplished to explore the impacts of seed priming of Si-NPs on wheat (Triticum aestivum L.) growth and yield under different drought levels. The plants were grown in pots under natural ecological environmental conditions and were harvested on 25th of April, 2020. The results revealed that seed priming of Si-NPs (0, 300, 600, and 900 mg/L) suggestively improved, the spike length, grains per spike, 1000 grains weight, plant height, grain yield, and biological yield by 12-42%, 14-54%, 5-49%, 5-41%, 17-62%, and 21-64%, respectively, relative to the control. The Si-NPs improved the leaf gas trade ascribes and chlorophyll a and b concentrations, though decreased the oxidative pressure in leaves which was demonstrated by the diminished electrolyte leakage and upgrade in superoxide dismutase and peroxidase activities in leaf under Si-NPs remedies over the control. The outcomes proposed that Si-NPs could improve the yield of wheat under a dry spell. In this manner, the utilization of Si-NPs by seed priming technique is a practical methodology for controlling the drought stress in wheat. These findings will provide the basis for future research and helpful to improve the food security under drought and heat related challenges.

Impacts of the COVID-19 pandemic on landfilling and recycling in the city of Fargo, North Dakota, USA.

The COVID-19 pandemic impacted different aspects of human lifestyle, including waste generation and management. The landfilled and recycled waste volume from the City of Fargo's annual solid waste report between 2019 and 2021 was critically analyzed to understand these impacts. The analysis showed a 4.5% increase in the residential waste volume in 2020 compared to 2019 and 2021, suggesting a pandemic-induced lockdown effect. The monthly residential waste volume was approximately 5-15% greater during the mandatory quarantine period (April - November 2020) than in 2019 and 2021. Commercial waste volume decreased by 12% during 2020 and then sharply increased in 2021 as commercial facilities reopened. The total recycling volume increased slightly by 2.5% in 2020 compared to 2019 and 2021. Cardboard recycling showed a 5.8% increase in 2020 from 2019 and a 13% increase in 2021 compared to 2020. This was presumably caused by the reliance on online shopping during the pandemic and becoming habituated to online shopping. The COVID-19 pandemic did not significantly impact other classes of recycled waste volumes. In summary, COVID-19 affected landfilling and recycling in different capacities in the City of Fargo. The data will contribute to the global understanding of the impact of COVID-19 on solid waste management practices.Implications: The COVID-19 pandemic impacted waste generation and management. In Fargo, USA, the monthly residential waste volume increased by up to 15% during the mandatory quarantine period in 2020 compared to the same period in 2019 and 2021. Conversely, the monthly commercial waste volume decreased during the mandatory quarantine period in 2020. The commercial waste volume increased in 2021 as commercial activities became normal. The cardboard recycling increased significantly because people became used to online shopping during the lockdown, and the practice continues. The findings will contribute to the global understanding of the impact of COVID-19 on solid waste management practices.

Source, occurrence, distribution, fate, and implications of microplastic pollutants in freshwater on environment: A critical review and way forward.

The generation of microplastics (MPs) has increased recently and become an emerging issue globally. Due to their long-term durability and capability of traveling between different habitats in air, water, and soil, MPs presence in freshwater ecosystem threatens the environment with respect to its quality, biotic life, and sustainability. Although many previous works have been undertaken on the MPs pollution in the marine system recently, none of the study has covered the scope of MPs pollution in the freshwater. To consolidate scattered knowledge in the literature body into one place, this work identifies the sources, fate, occurrence, transport pathways, and distribution of MPs pollution in the aquatic system with respect to their impacts on biotic life, degradation, and detection techniques. This article also discusses the environmental implications of MPs pollution in the freshwater ecosystems. Certain techniques for identifying MPs and their limitations in applications are presented. Through a literature survey of over 276 published articles (2000-2023), this study presents an overview of solutions to the MP pollution, while identifying research gaps in the body of knowledge for further work. It is conclusive from this review that the MPs exist in the freshwater due to an improper littering of plastic waste and its degradation into smaller particles. Approximately 15-51 trillion MP particles have accumulated in the oceans with their weight ranging between 93,000 and 236,000 metric ton (Mt), while about 19-23 Mt of plastic waste was released into rivers in 2016, which was projected to increase up to 53 Mt by 2030. A subsequent degradation of MPs in the aquatic environment results in the generation of NPs with size ranging from 1 to 1000 nm. It is expected that this work facilitates stakeholders to understand the multi-aspects of MPs pollution in the freshwater and recommends policy actions to implement sustainable solutions to this environmental problem.

COVID VS. NON-COVID Age-Specific Mortality In Islamabad: A Comparative Cross-Sectional Survey.

BACKGROUND: COVID-19 the ongoing pandemic. Mortality due to other reasons, other than COVID-19 across age groups reduced which was anecdotally reported from Pakistan. This survey was undertaken to assess the number of deaths recorded in Islamabad from 1st March 2019 to 30th May 2019 and from 1st March 2020 to 30th May 2020 and compare the two estimates by age and gender while documenting the cause of deaths. METHODS: The cross-sectional study was conducted in the Islamabad from 11th to 16th June 2020, comprising of secondary data received on age, gender, cause of death and months of death from the both, large private-public hospitals records and graveyards registers. Data was entered in both SPSS and Microsoft Excel and analysed using SPSS 22. RESULTS: The total number of hospitals and graveyards approached in ICT were 14 and 4 respectively. The total number of deaths reported from these during March to June in 2019 and 2020 were 2,389; out of which 1,225 (51.3%) deaths were recorded in 2019 and 1,162 (48.6%) deaths in 2020. In both years, predominant variables with more mortality were both age and gender between 61-70 years of age 511 (21.4%) 1,395 (58.4%) males respectively. CONCLUSIONS: More deaths were reported in males with old age. Cardio vascular diseases and neurological disorders were the leading causes of mortality. Not much of a larger difference in number of deaths between the both years was seen. Scarcity of data and unavailability of evidence make the anecdotal reports mere just a rumour.

Biofortification of Cereals and Pulses Using New Breeding Techniques: Current and Future Perspectives.

Cereals and pulses are consumed as a staple food in low-income countries for the fulfillment of daily dietary requirements and as a source of micronutrients. However, they are failing to offer balanced nutrition due to deficiencies of some essential compounds, macronutrients, and micronutrients, i.e., cereals are deficient in iron, zinc, some essential amino acids, and quality proteins. Meanwhile, the pulses are rich in anti-nutrient compounds that restrict the bioavailability of micronutrients. As a result, the population is suffering from malnutrition and resultantly different diseases, i.e., anemia, beriberi, pellagra, night blindness, rickets, and scurvy are common in the society. These facts highlight the need for the biofortification of cereals and pulses for the provision of balanced diets to masses and reduction of malnutrition. Biofortification of crops may be achieved through conventional approaches or new breeding techniques (NBTs). Conventional approaches for biofortification cover mineral fertilization through foliar or soil application, microbe-mediated enhanced uptake of nutrients, and conventional crossing of plants to obtain the desired combination of genes for balanced nutrient uptake and bioavailability. Whereas, NBTs rely on gene silencing, gene editing, overexpression, and gene transfer from other species for the acquisition of balanced nutritional profiles in mutant plants. Thus, we have highlighted the significance of conventional and NBTs for the biofortification of cereals and pulses. Current and future perspectives and opportunities are also discussed. Further, the regulatory aspects of newly developed biofortified transgenic and/or non-transgenic crop varieties via NBTs are also presented.

Assessment of grain yield indices in response to drought stress in wheat (Triticum aestivum L.).

Drought stress constricts crop production in the world. Increasing human population and predicted temperature increase owing to global warming will lead ruthless problems for agricultural production in near future. Hence, use of high yielding genotypes having drought tolerance and scrutinize of drought sensitive local cultivars for making them tolerant may be the proficient approaches to cope its detrimental outcomes. The current study was executed during 20015-2016 and 2016-2017 in field using randomized complete block design under factorial arrangements on 50 wheat genotypes for exploring their sensitivity and tolerance against drought. Some of the attributes of grain yield and drought tolerance indices were recorded. Grain yield showed negative correlations with tolerance index (TOL), drought index (DI) and stress susceptibility index (SSI) while positive correlation with mean productivity (MP) and geometric mean productivity (GMP) under drought condition. These findings depicted that tolerant genotypes could be chosen by high MP and GMP values and low SSI and TOL values. Based on the results, genotypes GA-02, Faisalabad-83, 9444, Sehar-06, Pirsabak-04 and Kohistan-97 were more tolerant and recognized as suitable for both normal and drought conditions. Genotypes of Chenab-00, Kohsar-95, Parwaz-94 and Kohenoor-83 confirmed more sensitive due to high grain yield loss under drought stress.

A Large Grade 5 Mobile Aortic Arch Atheromatous Plaque: Cause of Cerebrovascular Accident.

Aortic atheromas (aortic atheromatous plaques) are defined by an irregular thickening of the intima ≥2 mm, and a complex plaque is defined as a protruding atheroma ≥4 mm with or without an attached mobile component. Stroke incidence is approximately 25% in patients with mobile plaques of the aortic arch and 2% in patients with quiescent nonmobile plaques. Antiplatelet agents, oral anticoagulants, and statins have been suggested in the management of atheromas. We present an 80-year-old male, with non-ST-segment elevation myocardial infarction (NSTEMI) and chronic dysarthria, found to have an acute cerebrovascular accident (CVA) secondary to embolism from a large 12 mm aortic arch plaque, treated medically with oral antiplatelet therapy, anticoagulation, and statin therapy.

Hematopoietic stem cell transplantation for adult sickle cell disease in the era of universal donor availibility.

Current projections estimate that the number of newborns with sickle cell disease (SCD) globally will exceed 400,000 by 2050. Over the last three decades, increased newborn screening, supportive care, and use of hydroxyurea therapy, have decreased early childhood mortality among individuals affected with SCD. Despite hematopoietic cell transplantation (HCT) being curative in SCD, its impact on disease free survival remains unknown, especially in adults, partly due to previous limitations in donor options and perceived mortality in adults using myeloablative conditioning. Novel non-myeloablative or reduced intensity conditioning regimens have made HCT safer and applicable to adults with SCD who were previously excluded. Other reasons for limited use of HCT in SCD includes referral bias, provider preference, poor education of patient/families, perceived procedure risks, costs and limited logistic resources in both low income, middle income, and high income countries. Current data from landmark studies indicate that both the long-term disease-free survival and overall survival exceed 90% after matched sibling donor HCT in children. Improving transplant outcomes and expanding donor pool will increase the use of transplant for SCD, especially in affected adults. On-going investigations using matched umbilical cord units, unrelated matched donor, and related haploidentical donors, promises to make HCT a viable option for nearly all eligible patients with SCD. This systematic review focuses on the recent data for HCT for patients with adult SCD with particular emphasis on donor sources and availability as illustrated by a case presentation exhibiting real world issues.

Haploidentical Stem Cell Transplantation: A Gateway to Infrequent Availability of HLA-Matched Related Donors.

Haploidentical stem cell transplantation provides a plausible alternative for the patients when a fully matched donor is unavailable. Historically, the decision of considering haploidentical transplant has remained elusive; however, with the recent advances, the consideration of haploidentical grafts as a treatment option has become more apparent for both allografting for diseases and engraftment failure. We are reporting here an anecdotal case of a successful haploidentical engraftment in a patient with the prior graft failure of an HLA-matched related donor. Since the patient was severely alloimmunized, desensitization protocol was utilized before the haploidentical transplant, and the patient after 8 months of her second allogeneic transplantation is doing great with successful engraftment, no relapse, and no graft-versus-host disease (GVHD). Numerous reports pertinent to haploidentical graft have shown favorable outcomes in the graft placement, a decline in the rate of GVHD, and an improvement in the morbidity and mortality in affected individuals. Based on the current reports, haploidentical transplantation might be more feasible and has meaningful implications in the situations where matched donors are infrequent.

Orbital dermatofibrosarcoma protuberans with intracranial extension preceded by recurrent leiomyoma of the orbit: a case report.

INTRODUCTION: Dermatofibrosarcoma protuberans is a rare, locally aggressive cutaneous tumor of intermediate to low-grade malignancy. COL1A1-PDGFß translocation is specific to dermatofibrosarcoma protuberans, where the abnormally fused COL1A1-PDGFß gene directs formation of an abnormal combined (fusion) protein that researchers believe to ultimately function like the platelet-derived growth factor-beta protein. CASE PRESENTATION: In this report, we present a case of a 63-year-old Asian man with dermatofibrosarcoma protuberans of the right orbit with intracranial extension. He had a prior history of recurrent leiomyomas at the identical site. He underwent near-total en bloc resection of the tumor through a wide craniectomy with a 6 cm rim of the frontal scalp, allowing the tumor to be resected en bloc, leaving negative margins. Microscopically, the tumor comprised spindle cells with mild nuclear atypia and a low mitotic index embedded in a spiraling pattern of decussating fascicles consistent with dermatofibrosarcoma protuberans. The lesion was positive for CD34 and BCL2. Following resection, the patient was started on imatinib mesylate therapy (800 mg/day). CONCLUSIONS: We propose that platelet-derived growth factor, which has been implicated in the progression of leiomyomas by augmenting mitogenesis, may have acted in an autocrine manner to cause cell division, which may have led to the development of dermatofibrosarcoma protuberans in our patient. Further research is imperative to find certain molecular associations between the discussed soft tissue tumors. Also important is the effective utilization of platelet-derived growth factor receptor kinase inhibitors to prevent transformation to any platelet-derived growth factor-driven tumor, which in our patient was a dermatofibrosarcoma protuberans.

Harmful effects of shisha: literature review.

Tobacco is a preventable cause of morbidity and mortality across the world. A recently infamous way of smoking tobacco is shisha. Shisha smoking is also known as water pipe, hookah and Narghile smoking. The percentage of shisha smokers is on the rise rapidly spanning the globe. A literature review was conducted to identify all evidence on the epidemiological variations and health effects of shisha smoking. "Pub med" is used as a searching tool to identify all relevant empirical studies conducted worldwide. A qualitative overview of evidence is presented. Exposure to Shisha smoking is significantly associated with low infant weight, heart rate variations, hyperglycemia and hypertriglyceridemia. Increased risk of carcinoma is also leagued with it including carcinomas of the pancreas and lung being at the forefront. In conclusion, this review identifies grounds of several adverse conditions being associated with the habit of shisha smoking. It also evaluates the relevant epidemiological variations around the globe. The review culminates in the importance of enlightening shisha smokers regarding its deleterious effects.