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Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

The COVID-19 era marked one of the most alarming periods in history. In 2020, medical science had limited knowledge about the virus, leading to escalating morbidity and mortality rates. Consequently, many individuals turned to herbal medicines for potential solutions. The composition of these herbal remedies remained unknown during that period. Unfortunately, many of them contained hazardous heavy metals such as arsenic. In countries like India, where a substantial portion of the population relies on herbal treatments, incidents of exposure to toxic heavy metals have surged. We report a case series in which a family of five members consumed herbal medicine for COVID-19 prevention, inadvertently causing arsenic toxicity in the entire family. The ingredients of herbal remedies remain undisclosed and can lead to poisoning if not identified promptly, thus timely diagnosis is crucial. This case series showcases the diverse challenges linked to herbal products, underlining their potential influence on the causes of patients’ morbidity and mortality.

Cardiac tamponade is a life-threatening condition caused by the accumulation of blood or fluid between the pericardial sac and the heart. The excessive pressure on the heart in cardiac tamponade results in a rapid drop in blood pressure and impairs its ability to function properly. Without timely treatment, cardiac tamponade can lead to death due to its detrimental effects on the heart and overall circulation. In this case study, we reported two cases of middle-aged males in their 60s who sought emergency medical attention due to the onset of acute and intense chest pain accompanied by respiratory distress. Upon conducting an autopsy, profound atherosclerotic changes were identified in major blood vessels. Furthermore, a substantial volume of clotted blood was discovered within the pericardial sac, accompanied by a tear in the ventricular wall. However, cardiac tamponade cases are rare in forensic medicine practice, the classic indicators of hemopericardium and ventricular wall rupture can distinguish the condition.

•Multiple mechanisms drove CD22 antigen escape, including epitope loss (protein truncation, protein destabilization) and epitope alteration.•Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

T-lymphoblastic lymphoma and thymoma are distinct primary mediastinal neoplasms that can have similar clinical presentations and overlapping histological features. Microscopic distinction is occasionally difficult because the immature lymphocytes associated with thymoma may resemble T-lymphoblastic leukaemia/lymphoma cells, morphologically and immunohistochemically. An accurate diagnosis assumes particular importance since the treatment approaches for these two entities differ considerably. Multimodality diagnostic approaches incorporating histological, flow cytometry immunophenotypic‚ and molecular approaches are required. In this article, we describe four patients, each presenting with a mediastinal tumour in different clinicopathological settings. A detailed report of each case will follow, illustrating the challenges involved in the diagnosis in patients with these mediastinal neoplasms.

ABSTRACTThe left angular gyrus (AG) is thought to play a critical role in episodic retrieval and has been implicated in the recollection of specific details of prior episodes. Motivated by recent fMRI studies in which it was reported that elevated neural activity in left AG during study is predictive of subsequent associative memory, the present study investigated whether the region plays a causal role in associative memory encoding. Participants underwent online transcranial magnetic stimulation (TMS) while encoding word pairs prior to an associative memory test. We predicted that TMS to left AG during encoding would result in reduced subsequent memory accuracy, especially for estimates of recollection. The results did not support this prediction: estimates of both recollection and familiarity-driven recognition were essentially identical for words pairs encoded during TMS to left AG relative to a vertex control site. These results suggest that the left AG may not play a necessary role in associative memory encoding. TMS to left AG did however affect confidence for incorrect ‘intact’ judgments to rearranged pairs and incorrect ‘rearranged’ judgments to intact pairs. These findings suggest that the left AG supports encoding processes that contribute to aspects of subjective mnemonic experience.

Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state. Combination therapy reduced the frequency of these subsets, while simultaneously inducing a separate polyfunctional inflammatory TAM subset cosecreting TNF-α, IL-6, and IL-12. Tumor suppression by this combined therapy was partially dependent on T cells, and on TNF-α and IFN-γ. Together, this study demonstrates the potential for targeting TAMs to convert a “cold” into an “inflamed” tumor microenvironment capable of eliciting protective T cell responses.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI. Clinical findings and histopathologic features of lymph nodes were assessed in 70 patients with BI-ALCL. LNI was defined by the histologic demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had LNI, all lymph nodes involved were regional, the most frequent were axillary (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often associated with perifollicular, interfollicular, and diffuse patterns. Two cases had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49 (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI achieved complete remission after various therapeutic approaches. Two of 14 (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is associated with a higher risk of LNI. Involvement of lymph nodes was associated with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.

Acute myeloid leukemia (AML) stem cells (AMLSCs) AMLSCs and residual cytarabine (AraC)-resistant AML cells (constituting minimal residual disease, MRD) thought to be responsible for chemoresistance and treatment failure, were shown to be highly dependent on mitochondrial function for survival and thus are vulnerable to pharmacological blockade of the oxidative phosphorylation (OXPHOS) (Farge et al. Cancer Discov, 2017). Efficacy of OXPHOS inhibitor IACS-010759 (OXPHOS-i) was previously reported, demonstrating potent inhibition of mitochondrial complex I, OXPHOS suppression and growth inhibition of AML cells (Molina, et al. Nat Med, 2018). Here we evaluated OXPHOS dependency of AML MRD cells and determined impact of OXPHOS blockade on residual AML cells surviving standard chemotherapy (Doxorubicin/AraC, DA). Our results demonstrated that AML cell lines treated with AraC or DA induced accumulation of reactive oxygen species, mitochondrial superoxides, increased mitochondrial mass and mitochondrial membrane potential. AraC- and DA therapies in vitrowere significantly enhanced by OXPHOS-i. OXPHOS dependency shown as a significantly increased basal and maximal oxygen consumption rate after AraC and DA treatment, was fully inhibited by OXPHOS-i, leading to complete mitochondrial collapse. OXPHOS inhibition in combination with DA translated into reduction of viable cell numbers, induction of apoptosis and differentiation in AraC-sensitive and AraC-resistant cell lines models. In vitroefficacy was also observed in engineered p53-mutated MOLM13 model, indicating that combination of OXPHOS-i and DA might successfully overcome p53 mutation-driven chemoresistance. These effects were further validated in a subset of AraC-resistant primary patient samples. Mechanistically, induction of ROS caused by OXPHOS-i addition upon DA contributed to differentiation and cell death, and was partially reversed by ROS scavengers.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and aggressive variant of large B-cell lymphoma. A substantial subset of THRLBCL patients (pts) relapse after frontline anthracycline-based therapy. There is a scarcity of outcome data on therapy options for relapsed/refractory (r/r)THRLBCL, particularly CD19 CAR-T therapy.A recent genetic and spatial analysis provided critical insights into the complex interactions at the tumor-immune interface in THRLBCL. Understanding the mechanisms by which tumor cells evade the immune system is crucial in designing treatment strategies. This retrospective study aims to analyze clinicopathologic data in pts with r/r THRLBCL with the goal of identifying patterns that may influence response rates and long-term survival.

Understanding the factors influencing survival in oldest old population is crucial for providing appropriate care and improving outcomes. This prospective observational study aimed to investigate the determinants of survival in acutely ill oldest old patients during acute hospitalization and 1-month follow-up. Various geriatric domains and biochemical markers were assessed. Among the 70 included patients with a median age of 87 (Inter quartile range: 85–90), the presence of diabetes, delirium, tachypnea, and high sirtuin-5 levels were associated with reduced in-hospital survival. Non-survivors had raised levels of Sirtuin 1 and Sirtuin 5, with an increase of 43% and 70%, respectively. At 1 month, delirium and diabetes were still associated with reduced survival. These findings suggest that type-2 diabetes, delirium, tachypnea, and high sirtuin-5 levels could serve as predictors of reduced survival in acutely ill, hospitalized oldest old patients.

Background: Over the last four decades, tremendous growth has been witnessed in the field of electrically conducting polymers. A great deal of theoretical and empirical efforts have been made to achieve multifunctional conducting polymeric structures. However, the major challenge in this field is achieving the minimum band gap value which governs various electronic and optoelectronic properties of the structure. Objective: Artificial optimization viz., metaheuristic algorithms have been clubbed with the polymer problem to investigate the electronic properties of copolymers. Method: Band structures of different homopolymers obtained from ab-initio Hartree-Fock crystal orbital method have been used as input to obtain the electronic properties of copolymers using genetic algorithm, ant colony optimization and particle swarm optimization. Result: Nature-based computing methods employed for tailoring intrinsically conducting copolymers correspond to optimal electronic properties. Conclusion: This computational cloning approach provides a cost-effective and potent passage for taking forward optimized theoretical solutions to synthetic environment.

AimsT cell prolymphocytic leukaemia (T-PLL) is defined as an aggressive T cell leukaemia composed of small to medium-sized lymphocytes with a mature T cell immunophenotype. Most of these cases are known to be associated with inv(14q11q32)/t(14;14)(q11;q32) or rarely t(X;14)(q28;q11). However, T-PLL can show variations in clinical presentation, morphology or immunophenotype that can make a diagnosis of T-PLL challenging. We aim to explore the value of ancillary testing in the diagnosis of T-PLL.MethodsWith this large cohort of 69 patients with T-PLL, we compared the diagnostic utility of conventional cytogenetics, TCL1rearrangement by fluorescence in situ hybridisation (FISH) and TCL1 expression by immunohistochemistry (IHC).ResultsConventional karyotyping was performed in all 69 patients and was abnormal in 44 (65%), showing 14q32 abnormalities in 31 (43%) and t(X;14) (MTCP) in 2 (3%). TCL1rearrangement was assessed by FISH in 26 cases and was positive in 23 (85%). All cases with 14q32 abnormalities shown by karyotype were positive for TCL1rearrangement by FISH, whereas 12/15 (80%) cases without 14q32 abnormalities were also positive. TCL1 overexpression by IHC was detected in 51/64 (81%), including 40/42 (95%) cases with TCL1/14q32 rearrangement, and 3 cases without, showing a concordance of 89%. TCL1 IHC was negative in both cases with t(X;14)(q28;q11).ConclusionsOur study shows that TCL1 by IHC is a convenient test, positive in >80% T-PLL. Conventional cytogenetics is insensitive in the detection of 14q32/TCL1rearrangements but provides more complete information of the chromosomal landscape of T-PLL. FISH for TCL1rearrangement is very valuable in diagnostic challenging cases.

Particle swarm optimization has been integrated with the negative factor counting technique and inverse iteration method for efficient tailoring of quaternary low-bandgap copolymers. To analyze the performance of this methodology, model quaternary copolymers have been designed. Various parameters have been carefully selected while devising this methodology for engineering quaternary polymers. In particular, a swarm size of 40 has been chosen as it is found to impart good exploring skills to the algorithm. Also, the fitness function so chosen is found effective for judicious decision making. Verifying the reliability of this approach, quaternary D–A–D copolymers based on cyclopentadienylene, silole and thiophene donors, and dicyanomethylene and carbonyl acceptors respectively have been tailored. Cyclopentadienylene–carbonyl is obtained as the best D–A couple and is found to be highly desirable for designing low-bandgap polymeric skeletons. DOS curves of the investigated copolymers give a similar qualitative picture of the trends in the electronic properties as obtained from the algorithm. Such an in silico approach efficiently returns optimized results worthy of synthetic trials.

Acetaminophen toxicity is a leading cause of acute liver failure (ALF). We found that miRNA-122 (miR-122) is down-regulated in liver biopsy specimens of patients with ALF and in acetaminophen-treated mice. A marked decrease in the primary miR-122 expression occurs in mice on acetaminophen overdose because of suppression of its key transactivators, hepatocyte nuclear factor (HNF)-4α and HNF6. More importantly, the mortality rates of male and female liver-specific miR-122 knockout (LKO) mice were significantly higher than control mice when injected i.p. with an acetaminophen dose not lethal to the control. LKO livers exhibited higher basal expression of cytochrome P450 family 2 subfamily E member 1 (CYP2E1) and cytochrome P450 family 1 subfamily A member 2 (CYP1A2) that convert acetaminophen to highly reactive N-acetyl-p-benzoquinone imine. Upregulation of Cyp1a2primary transcript and mRNA in LKO mice correlated with the elevation of aryl hydrocarbon receptor (AHR) and mediator 1 (MED1), two transactivators of Cyp1a2. Analysis of ChIP-seq data in the ENCODE (Encyclopedia of DNA Element) database identified association of CCCTC-binding factor (CTCF) with Ahrpromoter in mouse livers. Both MED1 and CTCF are validated conserved miR-122 targets. Furthermore, depletion of Ahr, Med1, or Ctcfin Mir122−/−hepatocytes reduced Cyp1a2expression. Pulse-chase studies found that CYP2E1 protein level is upregulated in LKO hepatocytes. Notably, miR-122 depletion sensitized differentiated human HepaRG cells to acetaminophen toxicity that correlated with upregulation of AHR, MED1, and CYP1A2expression. Collectively, these results reveal a critical role of miR-122 in acetaminophen detoxification and implicate its therapeutic potential in patients with ALF.

Recollection – retrieval of qualitative information about a past event – is associated with enhanced neural activity in a consistent set of neural regions (the ‘core recollection network’) seemingly regardless of the nature of the recollected content. Here, we employed multi-voxel pattern analysis (MVPA) to assess whether retrieval-related functional magnetic resonance imaging (fMRI) activity in core recollection regions – including the hippocampus, angular gyrus, medial prefrontal cortex, retrosplenial/posterior cingulate cortex, and middle temporal gyrus – contain information about studied content and thus demonstrate retrieval-related ‘reinstatement’ effects. During study, participants viewed objects and concrete words that were subjected to different encoding tasks. Test items included studied words, the names of studied objects, or unstudied words. Participants judged whether the items were recollected, familiar, or new by making ‘remember’, ‘know’, and ‘new’ responses, respectively. The study history of remembered test items could be reliably decoded using MVPA in most regions, as well as from the dorsolateral prefrontal cortex, a region where univariate recollection effects could not be detected. The findings add to evidence that members of the core recollection network, as well as at least one neural region where mean signal is insensitive to recollection success, carry information about recollected content. Importantly, the study history of recognized items endorsed with a ‘know’ response could be decoded with equal accuracy. The results thus demonstrate a striking dissociation between mean signal and multi-voxel indices of recollection. Moreover, they converge with prior findings in suggesting that, as it is operationalized by classification-based MVPA, reinstatement is not uniquely a signature of recollection.

Neuroimaging data indicate that episodic memory (i.e., remembering specific past experiences) and episodic simulation (i.e., imagining specific future experiences) are associated with enhanced activity in a common set of neural regions, often referred to as the core network. This network comprises the hippocampus, parahippocampal cortex, lateral and medial parietal cortex, lateral temporal cortex, and medial prefrontal cortex. Evidence for a core network has been taken as support for the idea that episodic memory and episodic simulation are supported by common processes. Much remains to be learned about how specific core network regions contribute to specific aspects of episodic simulation. Prior neuroimaging studies of episodic memoryindicate that certain regions within the core network are differentially sensitive to the amount of information recollected (e.g., the left lateral parietal cortex). In addition, certain core network regions dissociate as a function of their timecourse of engagement during episodic memory (e.g., transient activity in the posterior hippocampus and sustained activity in the left lateral parietal cortex). In the current study, we assessed whether similar dissociations could be observed during episodic simulation. We found that the left lateral parietal cortex modulates as a function of the amount of simulated details. Of particular interest, while the hippocampus was insensitive to the amount of simulated details, we observed a temporal dissociation within the hippocampus: transient activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. Because the posterior hippocampal and lateral parietal findings parallel those observed during episodic memory, the present results add to the evidence that episodic memory and episodic simulation are supported by common processes. Critically, the present study also provides evidence that regions within the core network support dissociable processes.

Introduction:Eudragit is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives.Areas covered:In this review, the physicochemical characteristics and applications of different grades of Eudragit in colon-specific/enteric-coated/sustained release drug delivery and taste masking have been addressed.Expert opinion:Eudragits are amorphous polymers having glass transition temperatures between 9 to > 150oC. Eudragits are non-biodegradable, nonabsorbable, and nontoxic. Anionic Eudragit L dissolves at pH > 6 and is used for enteric coating, while Eudragit S, soluble at pH > 7 is used for colon targeting. Studies in human volunteers have confirmed that pH drops from 7.0 at terminal ileum to 6.0 at ascending colon, and Eudragit S based systems sometimes fail to release the drug. To overcome the shortcoming, combination of Eudragit S and Eudragit L which ensures drug release at pH < 7 has been advocated. Eudragit RL and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications. Cationic Eudragit E, insoluble at pH ≥ 5, can prevent drug release in saliva and finds application in taste masking.

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPLin >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1mutations but enrichment of ASXL1/SRSF2comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1and SRSF2comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.

Disproportionation propensity of salts (HCl, HBr, heminapadisylate) and adipic acid cocrystal of corticotropin releasing hormone receptor-1 antagonist was studied using model free kinetics. Using thermogravimetic weight loss profile or heat flow curves from differential scanning calorimetry, an activation energy plot for salts and cocrystal was generated based on model free kinetics. This activation energy of disproportionation provided qualitative information about the solid state salt stability. To ensure the stability throughout the shelf life, “prototype” formulations of salts and cocrystal in tablet form were stored at 40 °C and several water vapor pressures. Disproportionation kinetics were studied in these prototype tablet formulations using two-dimensional X-ray diffractometry. Formulations containing the adipic acid cocrystal or heminapadisylate salt did not show disproportionation of API when stored at 40 °C/75% RH for 300 days. On the other hand, formulations containing HCl or HBr salt disproportionated. Though isostructural, the disproportionation propensity of HBr and HCl salts was quite different. The HCl salt highlighted the important role that volatility of the counterion plays in the physical stability of the formulations. Solution state stability (i.e., in dissolution medium) of salts and cocrystal was also assessed and compared with solid state stability, by determining their solubility at different pH’s, and intrinsic dissolution rate.

Objective: Particle swarm optimization (PSO) algorithm has been clubbed with two numerical methods viz., negative factor counting (NFC) technique and inverse iteration method to investigate the electronic structures and properties of model polypeptide chains. Method: Band structures of polyglycine, polyalanine and polythreonine obtained from abinitio Hartree-Fock crystal orbital method using minimal basis (MB) set, double zeta (DZ) set and quasi-particle (DZ+QP) set respectively have been used as input to obtain the electronic properties of the model peptide sequences using the proposed computational procedure. Results: The results obtained indicate threonine to have strong influence over properties in comparison to alanine and glycine. Ternary sequences offer better electronic delocalization to the chain in comparison to the binary combinations. Better electronic properties are obtained with DZ basis set than with MB basis set. Also, it is found that with better electron correlation, the fundamental band gap value decreases by 3-4 eV. Conclusion: The density of states curves obtained using NFC technique is in good agreement with the PSO results. In all, coupling PSO algorithm with the otherwise computationally expensive quantum calculations not only fastens the process but also brings out useful output worthy of experimental investigations.

Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein–Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situhybridization; TP53mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vsnon-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2–295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (P<0.001), p53 positive by immunohistochemistry (P<0.001), CD30 negative (P<0.01), and of germinal center immunophenotype (P=0.01) compared with EBV-positive cases. No statistically significant difference in overall survival was identified based on EBV, TP53mutation status, germinal center vsnon-germinal center immunophenotype, or other immunohistochemical parameters evaluated. Patients who died of post-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (P<0.05). Our study demonstrates that diffuse large B-cell lymphoma-related immunohistochemical prognostic markers have limited relevance in the post-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant lymphoproliferative disorder.

Background and Objectives: The aim of the study is to evaluate the therapeutic efficacy and safety of Yttrium- 90 radiolabelled chimeric anti CD20 antibody-Rituximab in the treatment of patients with relapsed/ refractory B cell Non-Hodgkins Lymphoma (NHL). Methods: Twenty patients with relapsed/refractory CD20+ NHL in progressive state were included in the study. These patients had undergone a median of 2 (range 2-5) prior standard chemotherapy ± immunotherapy regimens. All the patients received rituximab 250 mg/m2 on days 1 and 8, and either 14 MBq/kg (0.4 mCi/kg) or 11 MBq/kg (0.3 mCi/kg) of Y-90 Rituximab on day 8 (maximum dose, 32 mCi) depending upon their platelet count. The patients were observed for systemic toxicity and response for at least 12 weeks after therapy. Results: No acute adverse effects were observed after the administration of 90Y-Rituximab. Overall response rate (ORR) was 45% of which complete response (CR) was observed in 2 patients, stable disease in 1 patient and partial response in 6 patients. The therapy was well tolerated with grade IV thrombocytopenia, neutropenia and anemia observed in 3, 4 and 2 patients respectively. Conclusion: 90Y-Rituximab therapy is safe and well tolerated in high risk extensively pretreated NHL patients. Toxicity is primarily hematologic, transient and reversible.

T-cell neoplasms are a highly heterogeneous group of leukaemias and lymphomas that represent 10–15% of all lymphoid neoplasms. Traditionally, our understanding of T-cell leukaemias and lymphomas has lagged behind that of B-cell neoplasms, in part due to their rarity. However, recent advances in our understanding of T-cell differentiation, based on gene expression and mutation profiling and other high throughput methods, have better elucidated the pathogenetic mechanisms of T-cell leukaemias and lymphomas. In this review, we provide an overview of many of the molecular abnormalities that occur in various types of T-cell leukaemia and lymphoma. Much of this knowledge has been used to refine diagnostic criteria that has been included in the fifth edition of the World Health Organization. This knowledge is also being used to improve prognostication and identify novel therapeutic targets, and we expect this progress will continue, eventually resulting in improved outcomes for patients with T-cell leukaemias and lymphomas.

History provided by the patient is the single most important step for initialization of anything that follows ahead to provide relief physically mentally or medico-legally. At times, deliberately and intentionally malingering is done by providing false, fabricated and cooked up history to the forensic clinical practitioner just to mislead in order to achieve secondary gains and rarely primary gain. As fabricated history leads to the wrong opinion which also misleads the court in administration of justice. For final medicolegal opinion and true history, the forensic clinical practitioner asks the details history of the victim and repeats the history after an external physical examination and also perusal the radiological reports, clinical records, and information be given by the police. This is a case of 29-year-old male who attended with an alleged history of being physically assaulted with the rod and firearm weapon, and history have given that he was shot by gun by his cousin's brother, one bullet was at left leg and two bullets at right leg and beat by the rod. In this case report author explained how to rule out the fabricated history and to make the fair medicolegal opinion truly based on the facts shoe in the external examination, radiological examination, and clinical records. The authors advised all forensic clinical practitioner that be aware and never rely completely on history given by the victim.

Occult and obscure bleeding are challenging conditions to manage, however recent advances in gastroenterology and endoscopy have improved our diagnostic and therapeutic capabilities. Occult gastrointestinal (GI) bleeding is non-visible bleeding detected solely by chemical tests or iron deficiency anemia. Obscure GI bleeding is an umbrella category of bleeding of unknown origin that persists or recurs after endoscopic evaluation of the entire bowel fails to reveal a bleeding source. This review details the evaluation of patients with occult and obscure GI bleeding and offers diagnostic algorithms. While treatment of GI bleeding depends on the type and location of the bleeding lesion, an overview of how to manage these conditions is presented.

It has been noted in the literature that there are increased complication rates following total hip arthroplasty (THA) in patients with chronic kidney disease (CKD) or end stage renal disease (ESRD). However, there is little data directly comparing outcomes in patients undergoing THA for osteoarthritis (OA) versus ESRD or CKD with OA. The objective of this study is to illustrate the risk of developing postoperative complications after THA in the CKD and ESRD populations by stage of disease when compared to a control group (OA) and thus better equip orthopaedic providers in the care of these patients.