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Exposure to methyl methane sulfonate (MMS), an alkylating agent, induces DNA damage, increasing cellular and metabolic sensitivity, leading to cellular demise and a delay in the cell cycle. This delay is attributed to changes in global transcription regulation, resulting in significant alterations in the proteome. Numerous studies have focused on transcriptome changes post-MMS treatment. However, cellular proteomic changes remain underexplored. This brief literature review is based on the assessment of studies obtained from several PubMed, Web of Science, and Scopus databases and Google Scholar using specific keywords. The article is based on manuscripts published between 2005 and 2024. Proteomic analysis identified 53 proteins, with 36 upregulated, 10 downregulated statuses, and a few exhibiting no or negligible changes. MMS exposure reflected changes in the phosphorylation status of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP-II) and a gross change in the transcriptome. Literature also supports the proteome change of the RNAP-II complex and ~1640 peptides, corresponding to 27 interacting proteins and the twelve RNAP-II subunits. The identified proteins were involved in DNA repair and energy pathway modulation. Notably, significant changes were observed in enzymes mostly related to carbohydrate and amino acid metabolism, predominantly, glycolysis, the fate of pyruvate, and the biosynthetic pathways of amino acid metabolism. The available literature supports a co-regulated response to MMS-induced DNA damage involving both DNA repair mechanisms and metabolic pathways.

Tuberculosis is a well-known endemic disease in India; however extra-pulmonary tuberculosis in the form of single parotid gland involvement is exceptionally unusual. Nevertheless, in instances involving slow-growing, prominent parotid gland enlargement, where malignancy is our major speculation, it should never be eliminated as a differential. There have been very few previously reported cases of tuberculosis involving salivary glands, and at times imaging has proven it difficult to diagnose such a condition and differentiate it from a benign mass or a malignancy. With that in mind, the authors present a case of tuberculosis involving just a single parotid gland in a 49-year-old woman who had been experiencing unilateral infra-auricular swelling and pain for a month. Apart from evening rise in temperature and generalised weakness, the patient had no additional symptoms suggestive of tuberculosis infection. Ultrasound represents the initial imaging modality of choice for assessment of the parotid gland. A sonographic examination of the authors’ patient revealed a diffusely enlarged left parotid gland with peripherally vascular hypo-echoic areas within. On contrast-enhanced CT the left parotid gland was seen to be replaced by a heterogeneously enhancing lesion, with an abscess-like appearance. The tubercular aetiology was established after a USG-guided tru-cut biopsy from the infra-auricular region revealed numerous loose granulomas with few langhans-type multinucleate giant cells amidst foci of necrosis and a salivary duct. Anti-TB medication was initiated for the patient subsequent to the presence of acid-fast bacilli on Ziehl-Neelsen staining. The patient has now received 3 months of AKT and there has been complete resolution of the symptoms.

Gastrointestinal stromal tumours (GIST) account for 1–3% of all the gastrointestinal (GI) neoplasms. It is the most common mesenchymal tumour in the Gl tract. The majority of GISTs are KIT gene positive; however, it is necessary to diagnose them pre-operatively. Here, the authors report the case of a 65-year-old male who presented with pain and a lump in the umbilical region for the last 2 years. On abdominal ultrasound, there was a heterogeneously hypoechoic mass in the umbilical region, with lobulated margins and central necrotic areas. On small bowel series, the core of the mass showed faint contrast opacification. Contrast-enhanced CT of the abdomen showed a heterogeneously enhancing, lobulated exophytic lesion arising from the small bowel loops, the central core of the lesion demonstrating an air-contrast level. Under ultrasound guidance, the lesion was biopsied. Histopathological findings were suggestive of a spindle cell tumour. The sample was c-KIT positive. Hence, the diagnosis of GIST was confirmed. The patient was given imatinib after resection of the mass. Usually, a GIST of larger size has higher malignant and metastatic potential; however, this article shows a gigantic small bowel GIST with cavitation and heterogeneity in different imaging modality, and still has no metastasis on imaging or high mitotic activity, and nuclear atypia on histopathology. A radiologist should also know the imaging pattern on conventional imaging and ultrasound, apart from usual cross-sectional imaging.

Chronic myelogenous leukemia (CML) results from neoplastic transformation of a hematopoietic stem cell. It is cytogenetically characterized by the presence of Philadelphia chromosome which results from reciprocal translocation t(9;22) that juxtaposes the ABL gene on chromosome 9 with breakpoint cluster region (BCR) on chromosome 22 generating BCR-ABL oncogene. All BCR-ABL fusion proteins display activated tyrosine kinase activity. Their different types are associated with different clinical course and prognosis. We report a rare case of e1a3 BCR-ABL transcript. So far only 4 cases in patients with CML have been reported. Key Words: BCR-ABL, e1a3, CML.

Abstract Background Osteopathia is a benign entity characterized by linear densities along the diaphysis and metaphysis of the longitudinal axes of the long bone. Parathyroid adenoma is a non-malignant parathyroid gland tumor characterized by increased parathormone levels, causing defecting calcium levels leading to multiple brown tumors, renal calculi, bone pains, polyuria, and arrhythmias in the patient. The coexistence of parathyroid adenoma with osteopathia striata has not been reported yet in the literature. To our knowledge, this is the first case of its kind. Case presentation An 18-year-old male patient presented to our institution with the complaint of genu valgum deformity in his right knee and was admitted for corrective surgery. While undergoing a preoperative evaluation, we came across multiple focal, lytic lesions in his radiographs and an atypical finding of osteopathia striata in his long bones. Further examination led us to the findings of cranial sclerosis and acro-osteolysis of distal phalanges. The tumor, whose catalyst was unclear, directed us toward an ultrasonographic analysis of the patient’s neck, leading us to a solitary parathyroid adenoma. Conclusions Radiological examinations played a very crucial role in the diagnosis of this condition. Though the reason behind osteopathia and the parathyroid lesion in this patient remains unknown, this presentation remains an exceptional and never-reported case of parathyroid adenoma and associated brown tumors in a patient with osteopathia striata.

Postpartum haemorrhage (PPH) is a significant cause of maternal morbidity and mortality. The management includes a spectrum ranging from mechanical and pharmacological to surgical methods. The authors report a case of a 24-year-old primigravida who presented with complaints of abdominal pain, distension, fever, and diarrhoea a few days after her delivery. She had postpartum haemorrhage, for which compression sutures were applied. On radiological investigations, she was diagnosed with myometrial necrosis, following which she underwent a subtotal hysterectomy. Myometrial necrosis is a common complication encountered in the setting of postpartum haemorrhage secondary to compressive sutures. An early diagnosis and an appropriate management requires adequate radiological investigations.

Background: In a developing country like India the cost effectiveness of all polyethylene tibial components is a major boon, without compromising the functional outcome. In this study we have attempted to evaluate the functional outcome of all polyethylene tibial monoblock component in total knee arthroplasty. Methodology: The study was carried out on 86 patients who are operated for total knee arthroplasty with all polyethylene tibial monoblock component. Demographic, surgical and follow up data was collected from case sheets of patients and copied in Performa. The patients were called for five years follow up and examined in the outpatient department. Results: The mean age of study population was 62.8 years (range 50 – 72 years) with mean BMI of 27.6 kg/m2. Statistically significant improvement was seen in the range of movements in all the age groups. Both male and female patients had insignificant difference in knee scoring. Assessment of clinical functional abilities of knee scoring have observed to be higher in patients with lower BMI. Conclusion: Significant improvement in range of motion as well as knee score in all age range, emphasizes the fact that total knee arthroplasty with all polyethylene design in osteoarthritis is an excellent surgery to restore near normal life style.

One of the primary uses of medicinal plants is as a diuretic. Both mono- and polyherbal-based diuretic formulations have been used in various parts of the world, including in India. One estimate states that more than 650 mono- and polyherbal formulations are in clinical use, including decoctions, tinctures, pills, and capsules made from over 75 plants. Many studies have been conducted supporting the diuretic properties of conventional herbal remedies. This article discusses many herbal plants from India that have historically been used as diuretics and identifies the chemical components with diuretic activity. In addition, this brief review also discusses several plant drugs and their pharmacological profile, concentrating on the administered dose and the bioactive extracts involved in the diuresis process. For researchers, searching for the best therapeutic plants for diuretic research may be a significant turning point in using various herbs from India.

Nerve abscess is an infrequently reported complication of leprosy. It is also an uncommon first manifestation of leprosy. In this case, due to the absence of classic signs and symptoms, such as skin lesions, hypoesthesia, and loss of sensation, the swelling was clinically diagnosed as a peripheral nerve sheath tumour on initial presentation. The authors have described an unusual presentation of pure neuritic leprosy that showcased nerve abscess. Clinical presentation was swelling over the medial aspect of the right arm and ulnar aspect of the right forearm, and clawing of the fourth and fifth digits of the right hand, with no signs of inflammation present on the skin surrounding the swelling. Hansen’s disease with pure nerve involvement could not be considered as a differential diagnosis solely based on clinical examination, therefore posing a diagnostic challenge. On ultrasonography, the right ulnar nerve showed diffuse intermittent thickening and a heterogeneously hypoechoic fusiform area with internal echoes at the site of swelling indicating a nerve abscess. These led the authors to the diagnosis of leprosy with perineuronal abscess. Histopathology confirmed the diagnosis by revealing granulomas and acid-fast Hansen’s bacilli. The patient showed dramatic response to surgery, multidrug therapy, and systemic corticosteroids.

Nickel-based coatings are well known for their good corrosion resistance performance. However, these materials suffer from inferior mechanical properties that limit their wider application. This work investigates the synthesis, and performs an exhaustive characterization, of Ni–P–B4C nanocomposite coatings developed through conventional electrodeposition using a modified Watts bath. The study examines the effect of an increase in the concentration of boron carbide nanoparticles (BCNPs) on the structural, morphological, topographical, mechanical and electrochemical properties of the nanocomposite coating. Vickers microhardness tester and nanoindentation technique were utilized to elucidate the role of BCNPs in modifying the mechanical response of nanocomposite coatings. Furthermore, corrosion resistance of the nanocomposite coatings was investigated through d.c potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). Comparison of the properties of the developed coatings revealed the remarkable improvement in the properties of Ni–P–B4C nanocomposite coatings when compared to the bare mild steel substrate and the Ni–P coatings. The enhanced corrosion resistance and superior mechanical properties of Ni–P–B4C nanocomposite coatings make them attractive for many industries. Based upon the experimental findings, a possible mechanism for the synthesis and improved corrosion resistance of Ni–P–B4C nanocomposite coatings was also proposed.

Background: Radiation exposure is an occupational hazard for interventional cardiologists and cardiac catheterisation laboratory staff that can manifest with serious long-term health consequences. Personal protective equipment, including lead jackets and glasses, is common, but the use of radiation protective lead caps is inconsistent. Methods: A systematic review qualitative assessment of five observational studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines protocol was performed. Results: It was concluded that lead caps significantly reduce radiation exposure to the head, even when a ceiling-mounted lead shield was present. Conclusion: Although newer protective systems are being studied and introduced, tools, such as lead caps, need to be strongly considered and employed in the catheterisation laboratory as mainstay personal protective equipment.

Here, the authors characterize a case of SARS-CoV-2 superinfection with Alpha and Epsilon variants, in which, via full genome sequencing analyses, they identify recombinant haplotypes in the spike, nucleocapsid, and ORF 8 coding regions, suggesting recombination could play a role in SARS-CoV-2 genetic diversity.

West and colleagues develop the Variant Database software tool for examination of changing Spike mutations in SARS-CoV-2 genomes. The authors use this to detect emerging lineages of SARS-CoV-2 in New York and report the rapid spread of the B.1.526 lineage in the city.

4-Chloro-1,2-phenylenediamine (4-Cl-OPD) is a halogenated aromatic diamine used as a precursor in permanent hair color production. Despite its well-documented mutagenic and carcinogenic effects in various in vitro and in vivo models, its role in fibrillar aggregate formation and their genotoxic effect in therapeutic proteins has received less attention. The significance of human serum albumin (HSA) arises from its involvement in bio-regulatory and transport processes. HSA misfolding and aggregation are responsible for some of the most frequent neurodegenerative disorders. We used various complementary approaches to track the formation of amyloid fibrils and their genotoxic effect. Molecular dynamics study demonstrated the complex stability. The impact of 4-Cl-OPD on the structural dynamics of HSA was confirmed by Raman spectroscopy, X-ray diffraction, HPLC and SDS-PAGE. Fibrilllar aggregates were investigated using Congo red assay, DLS, and SEM. The genotoxic nature of 4-Cl-OPD was confirmed using plasmid nicking assay and DAPI staining, which revealed DNA damage and cell apoptosis. 4-Cl-OPD provides a model system for studying fibrillar aggregation and their genotoxic potential in the current investigation. Future studies should investigate the inhibition of the aggregation/fibrillation process, which may yield valuable clinical insights.

Abstract Severe hypertension sometimes improves with treatment of bradycardia but this phenomenon is under‐reported. Here, an elderly gentleman with complete heart block and a hypertensive emergency was refractory to medical therapies and blood pressure only improved following pacemaker implantation. We discuss the possible mechanisms relating to heart rate and artificial pacing.

Tiantian Wang,1,2 Omar Moinuddin,1 Rebhi Abuzaitoun,1 Min Hwang,1 Cagri Besirli,1 Thomas J Wubben,1 David N Zacks1 1Department of Ophthalmology and Visual Sciences, University of Michigan W.K. Kellogg Eye Center, Ann Arbor, MI, USA; 2Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: David N ZacksUniversity of Michigan, Kellogg Eye Center, 1000 Wall St., Ann Arbor, MI, 48105 Tel +1 734-936-0871Email davzacks@umich.eduPurpose: To analyze the risk factors, clinical course, and visual and anatomic outcomes of retinal detachment (RD) after endophthalmitis.Patients and Methods: This retrospective study included 108 patients diagnosed with endophthalmitis between August 2014 and May 2019 at a single tertiary referral center. Sixteen patients developed RD after endophthalmitis. Retrospective analysis was performed to compare the cohort of endophthalmitis alone versus the cohort that developed RD after endophthalmitis, with analysis of potential risk factors for RD after endophthalmitis and treatment outcomes.Results: The incidence of RD after endophthalmitis was 14.8% (N=16/108). The median time to develop RD after endophthalmitis was 27 days (range: 1– 581 days, IQR: 25.3). Thirteen (81.3%) cases of RD occurred less than 2 months after the diagnosis of endophthalmitis. The incidence of aphakia (p=0.023) and posterior synechia (PS) (p=0.014) were significantly higher in the RD group. The mean initial and final visual acuity (VA) of the endophthalmitis alone group was 1.9± 0.8 logMAR and 1.2± 1.0 logMAR (p< 0.0001), respectively, and 1.9± 0.9 logMAR and 1.3± 1.2 logMAR (p=0.07) in the RD group, respectively. Enucleation or evisceration occurred in 31.3% of cases with RD after endophthalmitis. The rate of final retinal re-apposition for the RD cohort was 56.3%.Conclusion: The anatomic and functional outcomes for RD after endophthalmitis remain poor, with significant risk for permanent vision loss. Aphakia and posterior synechiae were seen more often in cases with RD after endophthalmitis.Keywords: pars plana vitrectomy, intraocular inflammation, aphakia, posterior synechiae, vision loss

Abstract In the present study, the effect of concentration of titanium carbide (TiC) particles on the structural, mechanical, and electrochemical properties of Ni–P composite coatings was investigated. Various amounts of TiC particles (0, 0.5, 1.0, 1.5, and 2.0 g L−1) were co-electrodeposited in the Ni–P matrix under optimized conditions and then characterized by employing various techniques. The structural analysis of prepared coatings indicates uniform, compact, and nodular structured coatings without any noticeable defects. Vickers microhardness and nanoindentation results demonstrate the increase in the hardness with an increasing amount of TiC particles attaining its terminal value (593HV100) at the concentration of 1.5 g L−1. Further increase in the concentration of TiC particles results in a decrease in hardness, which can be ascribed to their accumulation in the Ni–P matrix. The electrochemical results indicate the improvement in corrosion protection efficiency of coatings with an increasing amount of TiC particles reaching to ~ 92% at 2.0 g L−1, which can be ascribed to a reduction in the active area of the Ni–P matrix by the presence of inactive ceramic particles. The favorable structural, mechanical, and corrosion protection characteristics of Ni–P–TiC composite coatings suggest their potential applications in many industrial applications.

Katie X Li,1 Nicholas Carducci,1 Omar Moinuddin,1 Yunshu Zhou,1 David C Musch,1,2 David N Zacks,1 Cagri G Besirli,1 Thomas J Wubben1 1Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA; 2Department of Epidemiology, University of Michigan, Ann Arbor, MI, USACorrespondence: Thomas J WubbenDepartment of Ophthalmology and Visual Sciences, University of Michigan Medical School, 1000 Wall St, Ann Arbor, MI, 48105, USATel +1 734 936 8072Email twubben@med.umich.eduPurpose: To investigate the clinical features and surgical outcomes of rhegmatogenous retinal detachment (RRD) associated with giant retinal tears (GRTs) at a tertiary referral center.Patients and Methods: A retrospective, non-consecutive interventional case series of GRT-associated RRDs that underwent primary surgical repair at the University of Michigan W.K. Kellogg Eye Center between January 1, 2011 and July 1, 2020. Clinical characteristics and preoperative, perioperative, and postoperative data were collected.Results: Forty-eight eyes of 47 patients with GRT-associated RRDs met inclusion criteria, including those that were children (under 12 years, N=4, 8.3%), associated with a history of trauma (N=20, 41.7%) or with grade C proliferative vitreoretinopathy (PVR-C) (N=7, 14.6%) at baseline. Median age was 46 years (interquartile range (IQR): 29 years, range: 4 to 72 years), median follow-up was 28 months (IQR: 43 months, range: 3– 124 months), and 83.3% (N=40) of subjects were male. Primary surgical repair for GRT-associated RRDs included pars plana vitrectomy (PPV) (N=40, 83.3%), scleral buckle (SB) (N=1, 2.1%), or combined PPV/SB (N=7, 14.6%). Surgical approach commonly involved the use of perfluorocarbon liquid (N=43, 90%) and gas tamponade (N=39, 81%). Single surgery anatomic success (SSAS) was 75% (95% CI: 60%, 85%) at 3 months and 65% (95 CI: 47%, 78%) at 2 years. Final anatomic success was achieved in all 48 eyes (100%). Median visual acuity improved from 20/250 preoperatively to 20/60 at final follow-up, with 44% (N=20) of eyes achieving postoperative visual acuity of 20/40 or better.Conclusion: In this series from a tertiary referral center, both complex and non-complex GRT-associated RRDs were most commonly managed with PPV alone, perfluorocarbon liquid, and gas tamponade with favorable final anatomic and visual outcomes comparable to other modern GRT series.Keywords: giant retinal tear, proliferative vitreoretinopathy, retinal detachment, scleral buckle, trauma, vitrectomy

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70–80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.

Electrokinetics effectively removes contaminants, but its field-scale applications are limited mainly due to its high energy cost. In previous studies, the energy consumption was determined either by changing the soil’s specimens initial salt concentration while keeping the treatment time fixed or by changing the treatment time and keeping the same initial salt concentrations for all the specimens. Since both the initial salt concentration and treatment time are important parameters in determining reclamation cost, therefore, in this study, the soil specimens intentionally contaminated with different concentrations of sodium chloride (NaCl), i.e., varying from 3.7 to 15.5 g kg ^−1 , were exposed to a constant DC electric field of 1 V cm ^−1 for different time durations, i.e., varying from 6 to 72 h. The results show that electroosmotic flow (EOF) was directed from the anode to the cathode and higher for specimens contaminated with relatively low salt concentration, i.e., up to 7.6 g kg ^−1 . Therefore, for these specimens, due to the combined effect of electroosmosis and electromigration, the removal of Na ^+ was higher than the Cl ^− . However, for the specimen contaminated with a higher salt concentration, i.e., 15.5 g kg ^−1 , the Cl ^− removal exceeded Na ^+ due to the marginalization of EOF. Regardless of initial salt concentration, the electroosmotic flow and salt ions removal rates decreased with increasing treatment time, which might be attributed to the development of acidic and alkaline environments in soil. The collision of acidic and alkaline fronts resulted in a large potential gradient in a narrow soil region of pH jump, diminishing it everywhere else. This nonlinearity in the electric potential distribution in soil reduced the EOF and electromigration of salt ions.

This paper aims at analyzing the performance of reinforcement learning (RL) agents when trained in environments created by a generative adversarial network (GAN). This is a first step towards the greater goal of developing fast-learning and robust RL agents by leveraging the power of GANs for environment generation. The RL techniques that we tested were exact Q-learning, approximate Q-learning, approximate SARSA and a heuristic agent. The task for the agents was to learn how to play the game Super Mario Bros (SMB). This analysis will be helpful in suggesting which RL techniques are best suited for augmented experience training (with synthetic environments). This would further help in establishing a reinforcement learning framework using the agents that can learn faster by bringing a greater variety in environment exploration.

Background There is increasing utilization of cardiogenic shock treatment algorithms. The cornerstone of these algorithms is the use of invasive hemodynamic monitoring (IHM). We sought to compare the in‐hospital outcomes in patients who received IHM versus no IHM in a real‐world contemporary database. Methods and Results Patients with cardiogenic shock admitted during October 1, 2015 to December 31, 2018, were identified from the National Inpatient Sample. Among this group, we compared the outcomes among patients who received IHM versus no IHM. The primary end point was in‐hospital mortality. Secondary end points included vascular complications, major bleeding, need for renal replacement therapy, length of stay, cost of hospitalization, and rate of utilization of left ventricular assist devices and heart transplantation. Propensity score matching was used for covariate adjustment. A total of 394 635 (IHM=62 565; no IHM=332 070) patients were included. After propensity score matching, 2 well‐matched groups were compared (IHM=62 220; no IHM=62 220). The IHM group had lower in‐hospital mortality (24.1% versus 30.6%, P

Background There is a lack of contemporary data on cardiogenic shock (CS) in‐hospital mortality trends. Methods and Results Patients with CS admitted January 1, 2004 to December 31, 2018, were identified from the US National Inpatient Sample. We reported the crude and adjusted trends of in‐hospital mortality among the overall population and selected subgroups. Among a total of 563 949 644 hospitalizations during the period from January 1, 2004, to December 30, 2018, 1 254 358 (0.2%) were attributed to CS. There has been a steady increase in hospitalizations attributed to CS from 122 per 100 000 hospitalizations in 2004 to 408 per 100 000 hospitalizations in 2018 (Ptrend

Imran Moinuddin, Craig Fletcher, Peter MillwardDepartment of Pathology and Laboratory Medicine, Beaumont Hospital, Royal Oak, MI 48073, USACorrespondence: Imran MoinuddinDepartment of Pathology and Laboratory Medicine, Beaumont Hospital, 9190 Springfield Road, Apt. 27A, Poland 44514, OH, USATel +1 248 686 6255Email imranmoin80@yahoo.comBackground: Maternal red cell IgG antibodies can cross the placenta and cause hemolysis of fetal red cells in case of antigenic differences between maternal and fetal RBCs, leading to hemolytic disease of the fetus and newborn (HDFN). Although the incidence of anti-D associated HDFN has drastically reduced with Rh immune globulin prophylaxis, HDFN due to other maternal red cell alloantibodies still remains a concern. Prevalence and specificities of clinically significant red cell alloantibodies in pregnant females have rarely been reported in the USA.Methods: A retrospective chart review was conducted to determine the prevalence and specificity of clinically significant red cell alloantibodies in pregnant females who delivered at Beaumont Hospital Royal Oak between May 1, 2017 and December 31, 2017. A total of 4548 pregnant females were screened using electronic medical records. One female above 50 years age and two females with invalid ABO type were excluded from the study per IRB approved protocol. The remaining 4545 pregnant females with a valid ABO/RhD type and valid red cell antibody screen were included.Results: Out of the 4545 included females, 440 had a positive red cell antibody screen. Of these 440 females, 34 had clinically significant alloantibodies, giving an overall prevalence of 0.74%. Anti-E was the most frequently identified significant alloantibody followed by anti-K. The most prevalent significant alloantibodies in RhD positive and RhD negative females were anti-E and anti-K, respectively. Significant association (p-value

Purpose: The purpose of the study was to develop and optimize rosiglitazone maleate mucoadhesive extended-release tablets by quality by design (QbD) approach. Based on QTPP (quality target product profile) CQAs (critical quality attributes) were identified. Methods: Failure mode and effects analysis (FMEA) method were adopted for risk assessment. Risk analysis by the evaluation of formulation and process parameters showed that the optimizing the levels of polymers could reduce high risk to achieve target profile. Drug-excipient compatibility studies by Fourier transforms infra-red and DSC studies showed that the drug was compatible with the polymers used. Design of experiment (DoE) performed by Sigma tech software, Carbopol 934P and sodium carboxymethyl cellulose (SCMC) were identified as independent variables and hardness, drug release at 12 hours and ex vivo mucoadhesion time were adopted as responses. Contour plots generated from the software were used for identification of design space. Results: Carbopol 934P and SCMC had positive and negative effects respectively on the selected responses. Higher the concentration of Carbopol 934P and lower the concentration of SCMC mucoadhesive extended release criteria could be achieved. Drug release kinetics followed first order release with Higuchi diffusion and Fickian diffusion. Ex vivo mucoadhesion test on goat stomach mucosa indicated that adhesion time increased at higher concentrations of Carbopol 934P. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values, confirmed by calculating standard error. Conclusion: It has been concluded that the application of QbD in the optimization reduced the number of trials to produce a cost-effective formula.

Multivariate analysis was conducted to explore the moist temperate forests of the Shangla district, Khyber Pakhtunkhwa. The prime objective was to quantitatively describe and differentiate the vegetation groups and the factors that determine the boundaries and composition of plant communities in the Shangla district. This was achieved by sampling all common species in a complex vegetation mosaic coinciding with local gradients in topography and soil distribution. Ward’s clustering dendrogram demonstrated four significant vegetation clusters with respect to environmental effects. These four major groups of the tree vegetation were superimposed on the ordination plane: 1. Pinus wallichiana, the dominant group associated with Abies pindrow; 2. Abies pindrow and the Picea smithiana group; 3. Dominant Cedrus deodara associated with the Pinus wallichiana, Abies pindrow, Picea smithiana, and Quercus baloot group; 4. Pinus roxberghii pure group. The key controlling factors for each group were the environmental characteristics (i.e., edaphic factors, topographic factors, soil physical properties, and soil nutrients). The results revealed elevation (p p < 0.05) relationship with vegetation. The other environmental factor did not show a significant relationship with vegetation. Ward’s cluster dendrogram of understory species also demonstrated four groups. Group 1 comprises two subgroups, a and b, with the highest number of species, i.e., Digeteria sanguinalis, Fragaria nubicola, Verbascum Thapsus, Pinus wallichiana seedlings, and Polygonatum multiflorium, respectively. The second large group contains twenty-five species out of eight stands, and the dominant species was Tagetis minuta. Eighteen species out of six stands were found in group 3, which was considered the smallest group. Group 4 consisted of seven stands containing twenty-four species of ground flora, with Anaphalis scopulosa followed by Adiantum venustum as the dominant species. The environmental characteristics of the understory vegetation showed a resemblance with the tree communities. With the exception of elevation, the other factors did not show a significant correlation.

Stem cells can be defined as the cells that have the capacity to both self-renew and give rise to differentiated cells. Under the right conditions and signals, depending on their origin and bio-plasticity, stem cells can differentiate into multiple cell lineages and develop into various mature cells. Stem cell therapy is a fast-developing branch of medicine that includes the most innovative regenerative therapies for the restoration of cell and tissue function in individuals with severe diseases. Stem cell research has resulted in the emergence of cell-based therapies for disorders that are resistant to conventional drugs and therapies, and they are considered under the category of an Advanced Therapeutic Medicinal Product (ATMP). The FDA and the European Medicines Agency (EMA) devised a new strategy in 2017 with the aim of unifying the standards for development of ATMPs such that it is easy to exchange information at the international level. In this review, we discuss the evolution of mesenchymal stem cell-based therapy as an ATMP in the global and Indian scenarios, along with the guidelines governing their usage and clinical application of these therapeutics.