22 Other dopaminergic risk genes Three risk single nucleotide polymorphisms (SNPs) in the gene for the dopamine D2 receptor, DRD2, showed opposite effects in SB431542 patients and controls during a working memory task:

enhanced engagement of prefronto-striatal pathways in controls and reduced activity in patients,29 presumably because patients and controls are positioned on opposite Inhibitors,research,lifescience,medical sides of the inverted-u-shaped curve governing the relationship of dopaminergic simulation and prefrontal activity. On the postsynaptic side, Regulator of Gprotein signaling 4 (RGS4) modulates dopamine signal transduction by affecting G alpha-GTP binding. Allelic variation in RGS4 by itself modulated frontoparietal and frontotemporal activation

during working memory and was associated with frontal gray and white matter Inhibitors,research,lifescience,medical structural volume reductions.30 Further into the postsynapse, the pivotal integrator of information in dopaminoceptive neurons for the so-called canonical signal transduction pathway is dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), encoded by the gene PPP1R1B. A frequent PPP1R1B haplotype related to risk for schizophrenia predicted reduced striatal volume and activation Inhibitors,research,lifescience,medical (in good agreement with the expression profile of DARPP-32) and increased structural and functional connectivity of striatum with lateral prefrontal cortex in a large sample of genotyped healthy controls.31 Interestingly, genetic variation in AKT1, encoding another key signal transduction pivot, but now

for the non-canonical, beta-arrestin mediated dopaminergic pathway, Inhibitors,research,lifescience,medical similarly predicted reduced frontostriatal volume as well as inefficient prefrontal activation during working memory.32 Taken together, these two studies provide strong support for the prefrontoneostriatal system as a core circuit for dopaminergic variation related Inhibitors,research,lifescience,medical to schizophrenia risk. Investigating a panel of dopamine-related genes during a reward task,33 polymorphisms in DRD2 (141C deletion), DAT1 (9-repeat) and DRD4 (7-repeat), were related to ventral striatal activity, while COMT rs4680 was not, in agreement with its predominant role in prefrontal cortex activity. Genome-wide significant variants Despite their clear Cediranib (AZD2171) and often convergent impact on imaging phenotypes, the usefulness of candidate genes for understanding schizophrenia is debated because these a-priori hypothesized variants often show an inconsistent effect on the categorical disease phenotype itself. Genome -wide association studies (GWAS) offer an alternative, hypothesis-free way to identify genetic variants associated with the disease. While it is in our view unlikely that GWAS will provide all answers about common genetic variants impacting on schizophrenia, any variant that does survive the extreme amount of statistical thresholding that this method requires certainly merits study using intermediate imaging phenotypes.

In addition, most previous studies showing a significant relationship between LV dyssynchrony and FMR assessed

regional LV dyssynchrony from only 2 segments adjacent to the anterolateral and posteromedial PMs, while the present study assessed global LV dyssynchrony from 8 segments.12),19) This may be another probable reason for the discrepancy. While the geometric parameters of the mitral apparatus were estimated by using 2D echocardiography in the past studies,18-21) we performed these measurements with combined use of 3D echocardiography and MPR mode for 3D image analysis program Inhibitors,research,lifescience,medical in the present study. Taking that accurate measurement with high reproducibility is essential for the geometric measurement of small cardiac structures such as mitral apparatus into account, it is vital to obtain the same planes that cross identical portions of a certain structure, or Inhibitors,research,lifescience,medical intersect at a specific angle in every measurement, which is not guaranteed 2D echocardiography.

For this reason, geometric measurement of the MV or the tricuspid valve was performed under MPR guide in several previous studies.7),24-26) However, it is first trial to estimate the distances of both PMs using MPR in the present study. Using conventional 2D echocardiography, the PM distance was estimated by measuring the distance between the PM head and the contralateral Inhibitors,research,lifescience,medical mitral annular point on the apical 2 or 4 chamber plane. However, this method Inhibitors,research,lifescience,medical neither guarantees the same plane crossing the identical contralateral annular

point in every measurement nor provides two distances of both PMs. In our study, we first defined the PM distance using two anatomical landmarks (the distance from MJAM to the tip of each PM head). The plane displaying the two anatomical Inhibitors,research,lifescience,medical landmarks was then obtained using MPR. We expected it would be guaranteed to acquire the identical plane displaying the same point of the PM head in every measurement under MPR guide. However, intra-observer variability of PM distance measurement in the present study was less satisfactory than we expected. It was probably due to the cone shape of the PM head. The PM head displayed and in any cut plane always had the tip PI3K Inhibitor Library concentration because of its appearance of triangle. Therefore, it was a little perplexing to identify the same tip of the PM head repeatedly even under MPR guide. However, the reproducibility is expected to improve after certain period of time of learning curve. Study limitations In the present study, first, the study population was relatively small and the MR grade leaned to the mild to moderate MR. These might affect the results of the present study. Therefore, further investigations in larger population with more diverse degrees of MR and needed. Second, we assessed LV dyssynchrony from 8 segments of LV not 12 segments of LV. Third, we estimated MR severity without accounting the loading conditions that would modulate geometry of the LV and the mitral apparatus.

In our research program at Hillside Hospital, we have proposed that a naturalistic prospective research strategy can help to clarify the major developmental and clinical characteristics of the prodrome and answer many of the unresolved issues discussed above. The Hillside Recognition and Prevention (RAP) program The Recognition and Prevention (RAP) program of Hillside Hospital of the North Shore-Long

Island Jewish Health System in New York is designed to prospectively characterize the schizophrenia prodrome and evaluate a range of early interventions, including various psychosocial Inhibitors,research,lifescience,medical and psychopharmacological therapies. The program consists of the RAP clinic, which provides treatment for prodromal adolescents, and a number of related research projects. Since prevention involves both the accurate identification of vulnerable individuals and the administration of effective treatments, both Inhibitors,research,lifescience,medical are major foci of the program. In terms of selection, a major goal of the RAP program is to establish a predictor profile that will combine the most accurate neurocognitive and prodromal (behavioral) risk factors. With respect to treatment, our strategy is to first conduct a naturalistic Inhibitors,research,lifescience,medical study of treatment c-Met inhibitor effects. To do this, we currently treat “prodromal” symptoms as they would be treated

in the real world; in other words, treatment targets specific symptoms rather than attempting prevention. As a result, RAP clinic interventions do not necessarily involve antipsychotic medication. In fact, preliminary data collected from a recently completed 3year pilot study involving 50 prodromal adolescents have suggested that antidepressants Inhibitors,research,lifescience,medical are as effective as antipsychotics in improving overall level of functioning in individuals free of overt psychotic symptoms. By following a naturalistic

prospective study design Inhibitors,research,lifescience,medical and treatment strategy for a minimum of 5 years, we hope to pinpoint the therapies most appropriate for specific symptoms and developmental stages of the prodrome and to address many of the other questions raised in the discussion above. Our long-term goals are to establish a highly accurate system of early detection and to develop clinical trials on the basis of our naturalistic findings, and thus Mephenoxalone move increasingly closer to prevention.
Many advances have been made in the past decade in the treatment of schizophrenia. There have also been advances in the understanding the etiopathophysiology of schizophrenia, with much work studying neurochemical, neuroanatomical, genetic, and postmortem domains. New research has focused on early detection of schizophrenia, cognitive impairments, and improving long-term outcomes for patients who suffer from this devastating illness.1-3 Progress has been particularly due to a new class of medications the secondgeneration antipsychotics (SGAs), which have become available in the last 7 years.

Regarding the two studies only assessing effects on MDD, Zarate and colleagues undertook a cross-over RCT on 17 participants off Apoptosis inhibitor psychotropics for 2 weeks who received either ketamine or placebo saline infusion 1 week apart [Zarate et al. 2006]. Ketamine demonstrated a significant improvement over placebo at 24 hours (effect size

for drug difference d = 1.46; 95% confidence interval [CI] 0.91–2.01) and at 1 week (d = 0.68; 95% CI 0.13–1.23). Inhibitors,research,lifescience,medical A total of 71% of those administered ketamine met response criteria and 29% met remission criteria, measured on the HAMD, at 24 hours. Valentine and colleagues had a similar design, although in a smaller cohort (n = 10) and with a primary aim of evaluating changes in occipital Inhibitors,research,lifescience,medical amino acid neurotransmitters (discussed earlier in this paper) [Valentine et al. 2010]. They similarly found rapid antidepressant effects in the active group that were statistically significantly greater than that of the placebo group (HDRS score main effect of treatment (F(1,131) = 11.84, p < 0.0008). An earlier, but methodologically similar, study by Berman and colleagues included individuals with bipolar depression, although Inhibitors,research,lifescience,medical of the nine participants, only one had a bipolar depression, with the rest having a history of MDD [Berman et al.

2000]. At the time point 230 minutes post-ketamine infusion HAMD and HDRS scores displayed statistically significant improvements over placebo and 72 Inhibitors,research,lifescience,medical hours post-ketamine infusion

HAMD scores were reduced by an average of 48%. The two studies investigating the effect of ketamine in bipolar depression yielded similar positive results [DiazGranados et al. 2010b; Zarate et al. 2012]. Within 40 minutes of ketamine infusion, depressive symptoms significantly improved compared with placebo administration, remaining significant to day 3 in both studies (p < 0.001). DiazGranados and colleagues found an effect size of d = 0.52 (95% CI 0.28–0.76) at 40 minutes, d = 0.67 (95% CI 0.42–0.91) at 1 day and d = 0.22 (95% CI −0.03 to 0.48) at day 14 [DiazGranados et Inhibitors,research,lifescience,medical al. 2010b]. The largest effect size recorded by DiazGranados and colleagues was at 2 days post-infusion, d = 0.80 (95% CI 0.55–1.04). The work by Zarate and colleagues was with 14 subjects with treatment-resistant bipolar depression already stabilized mafosfamide on either lithium or lamotrigine who received either ketamine or saline infusions on two test days a fortnight apart [Zarate et al. 2012]. The authors reported a moderate to large drug effect size of d = 0.89 (95% CI 0.61–1.16) at 40 minutes through to 230 minutes (d = 0.85; 95% CI 0.57–1.14), at day 1 (d = 0.70; 95% CI 0.42–0.98) and at day 2 (d = 0.65; 95% CI 0.37–0.93), whilst the placebo showed no significant change in symptomatology. The largest effect size recorded by Zarate and colleagues was at 40 minutes post-infusion. Response rates were comparable at between 71% and 79%, as were remission rates of between 29% and 31%.

The authors have no relevant financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the Disclosure. No writing assistance was utilized in the production of this paper.
Globally defined as the application of nanotechnology to the clinical arena, Navitoclax purchase nanomedicine has its roots in the same basic concepts and principles of nanotechnology; that is, materials with the nanoscale features present unique characteristics, otherwise absent at a macroscopic level [1]. Just as nanotechnology benefits from mathematics

Inhibitors,research,lifescience,medical and engineering, nanomedicine too has a multidisciplinary nature involving notions and techniques borrowed Inhibitors,research,lifescience,medical from biology, chemistry, and physics [2]. As a result of this successful

marriage, nanostructure materials display emerging functions that have exceptional benefits when applied to medical devices. The success of nanotechnology in the healthcare sector is driven by the possibility to work at the same scale of several biological processes, cellular mechanisms, and organic molecules; for this reason, medicine has looked at nanotechnology as the ideal solution for the detection Inhibitors,research,lifescience,medical and treatment of many diseases. One of the many applications of nanotechnology to the medical sector Inhibitors,research,lifescience,medical is in the field of drug delivery. The advent of protocols and methods for the synthesis, functionalization, and use of nanoparticles

and nano-carriers has flooded the scientific and clinic community with new therapeutic approaches from molecular targeting to radiofrequency Inhibitors,research,lifescience,medical ablation and from personalized therapies to minimally invasive techniques. While most members of the investment community are able to grasp the meaning of nanotechnology and can expertly launch and manage a viable product into the market, they are limited in their conceptual understanding of this scientific discipline and the intricate inner workings behind the product’s functionality [3]. On the contrary, those involved in the scientific research recognize that first nanomedicine is an expansion of nanotechnology but have very little understanding of the business expertise required to develop their technologies into a commercial product [3]. Cooperation is therefore needed between the two factions in order to lead nanomedicine-based inventions to a successful market position. 2. Nanomedicine Market With 76% [4] of the publications and 59% [4] of the patents, drug delivery is the market segment that dominates the nanomedicine sector. In vitro diagnostics represent the second leading field, contributing with 11% [4] of the publications and 14% [4] of the patent filings.

It is most Dyngo-4a mw common in young adults, especially in women in poor economic areas.94 Mixed cellularity Hodgkin’s disease is more common in children and older adults in developing countries.4,11 Conclusion Peripheral LAP is a common finding in routine clinical

practice. When physicians are faced with it, the most serious task is to differentiate benign from malignant disorders. It Inhibitors,research,lifescience,medical is usually due to self-limited diseases, and most cases tend to subside without any sequel within a limited period, particularly in children. Some conditions require urgent attention and they include malignancy, TB, HIV infection, and immune-induced disorders such as systemic lupus erythematous, rheumatoid arthritis, Inhibitors,research,lifescience,medical and sarcoidosis. Special clues in the patient’s history and physical findings can help to select suitable work-up for

the patient. In general, lymph nodes are considered abnormal if their diameter exceeds one cm. However, there is no uniform nodal size at which the greater diameter can raise suspicion for a neoplastic etiology. The cervical region is the most frequent site involved in peripheral LAP at any age. Generalized LAP usually is indicative of an underlying Inhibitors,research,lifescience,medical disease. Some important causes include the Epstein-Barr virus, HIV, lymphoma, and autoimmune disorders. Ultrasound can assess the number, size, site, shape, margins, and pattern of vascularity and the internal structure of a lymph node. FNAC is more powerful in diagnosing metastatic cancers than lymphomas. Ultrasonography-guided FNAC offers more accurate information than does blinded FNAC. Needle biopsy can be used as the first step in the diagnostic approach to lymphomas, but excisional Inhibitors,research,lifescience,medical biopsy of enlarged lymph nodes is still the gold standard procedure. Age more than 40 years, multiple sites of LAP, supraclavicular lymph nodes, nodal diameter greater than 2 cm, firm or hard texture, fixed nodes, lack of tenderness,

and abnormal chest X-ray are factors that propel the physician into tissue sampling. If none of the predictive risks for malignancy is present, patients with peripheral LAP can be observed for 3 to 4 weeks before lymph node biopsy. Inhibitors,research,lifescience,medical Conflict of Interest: None declared.
Background: Sodium valproate (SV) has been approved for migraine prophylaxis and its intravenous form is used to treat acute migraine attacks. We compared the efficacy and safety of intravenous SV and subcutaneous Sumatriptan not in managing acute migraine attacks. Methods: This double-blind randomized clinical trial divided 90 patients into two groups: one group received 400 mg of intravenous SV and the second group received 6 mg of subcutaneous Sumatriptan. Headache severity before treatment and half an hour, one hour, and two hours after treatment was measured based on the VNRS in the groups. Associated symptoms, i.e., photophobia, phonophobia, nausea, and vomiting, were assayed on admission and 2 hours after treatment. Side effects of the drugs were checked 2 hours after injection.

In a separate study, we applied these molecular methods and established diversity and composition parameters to the analysis of microbial phylogeny in the oral, vaginal, and rectal microbiomes in gestational diabetes prior to onset of active labor.23 Microbial 16S rRNA was amplified by PCR using conserved regions. Samples were pooled into a single pyrosequencing Inhibitors,research,lifescience,medical run. QIIME pipeline was used to validate microbial 16S rRNA sequencing quality and assign sequences to the original specimens as above. Then, a basic local alignment search tool (BLAST) was used to identify OTU sequence homology in the bacterial

databases of the National Center for Biotechnology Information, to name specific genera and form a phylogenetic tree. Data indicate skewed prevalence

for multiple Inhibitors,research,lifescience,medical genera in either gestational diabetes or the healthy state, suggesting changes in microbial composition for the oral, vaginal, and rectal compartments in women with gestational diabetes when compared with healthy pregnancies (Table 1 and Figure 3). Table 1 Skewed microbial composition in oral, Inhibitors,research,lifescience,medical vaginal, and rectal compartments in normal versus gestational diabetes pregnancies. Figure 3 Oral, vaginal, and rectal phylogeny in normal pregnancies (NL) and gestational diabetes melitus (GDM). In conclusion, the microbiome of the urogenital tract plays an important role in health and disease,24,25 prompting more comprehensive study. In particular, relationships between obstetrical pathologies and the vaginal microbiome should be defined and causality differentiated from secondary ecosystem perturbations.23 Acknowledgments We are grateful to our clinical team for facilitating specimen procurement, Rob Knight Inhibitors,research,lifescience,medical for the use of the QIIME pipeline and help with data analysis,

Bruce Paster for advising oral microbiome analysis, and Siegfried Rotmesch for the use of the clinical facility and helpful discussions. Work was supported by a CCFA Senior Research Award #1832 (Offer Cohavy and Bruce Paster), and the Cedars-Sinai Research Institute. Abbreviations: OTU operational Inhibitors,research,lifescience,medical taxonomic units; PCR polymerase chain reaction; SPS sequences Dipeptidyl peptidase per specimen. Footnotes Conflict of interest: No potential conflict of interest relevant to this article was reported.
Ninety years after its JNK inhibitor introduction as an anti-epileptic treatment,1,2 and after periods of ups and downs in its use, the ketogenic diet (KD) has found its proper place in clinical practice. The idea of manipulating diets for therapeutic purposes has been around for centuries. For instance, fasting was used in the treatment of epilepsy since Biblical times (Matthew 17:5–21). The first modern reports of its use in the medical literature were by Guelpha in 1911 and Conklin in 1921.3 KD has been used to treat epilepsy in children since 1921 with little variation until recent years.

11,95 As a result, cytokines can potentially mediate both neuroprotective and neurotoxic processes at once. For example, ample evidence indicates that IL-iβ may exacerbate neuronal injury both in vivo and in vitro.96-99 In contrast, IL-iβ has also been implicated in neuroprotective processes such as remyelination,100 blood-brain barrier repair,101 ischemic tolerance,102 and neurotrophic factor production.103-106 Trametinib molecular weight Importantly, astrocytes can themselves respond to IL-iβ by releasing a number of potentially neuroprotective trophic factors such as nerve growth factor (NGF),

ciliary neurotrophic factor (CNTF), glial cell-line Inhibitors,research,lifescience,medical derived neurotrophic factor GDNF, and fibroblast growth factor (FGF)-2.11,107-109 Taken together, studies such as those mentioned above provide important information about the multiple effects of individual cytokines. However, they also have major limitations, in that they can only take into account a Inhibitors,research,lifescience,medical few pro- and anti-inflammatory pathways at a time. As such, they may only reflect a small fraction of an infinitely more intricate

process in which astrocytes take part. For this reason, the use of genetically manipulated animal models specifically preventing the proliferation of reactive astrocytes or the activation of their core inflammatory pathways, Inhibitors,research,lifescience,medical has provided important new insight into their overall role in Inhibitors,research,lifescience,medical response to brain injury. For instance, it has been demonstrated that the selective attenuation of astrocytic proinflammatory processes, through genetic inactivation of the transcription factor NF-kB specifically in this cell type, affords substantial neuroprotection following spinal cord

injury.110 By contrast, using a transgenic mouse model in which dividing reactive astrocytes were selectively Inhibitors,research,lifescience,medical ablated, Sofroniew and colleagues have demonstrated that following various types of brain injury, reactive astrocytes play an essential role in temporally and spatially restricting neurointlammation, as well as in promoting blood-brain barrier repair, limiting brain edema, and preserving neuronal viability.94,111-113 Consistent with a role of astrocytes in containing neuroinflammation, it is interesting to note that astrocytes appear to participate in the suppression of microglial Parvulin activation through negative feedback loops. Activated microglial cells release high levels of proinflammatorycytokines and toxic ROS which may negatively impact neuronal survival.114 Several in vitro studies have demonstrated that astrocyte-conditioned medium or the presence of astrocytes attenuates microglial activation in response to various proinflammatory stimuli.115-117 The exact nature of the astrocyte-derived factors involved has not been fully elucidated, but transforming growth factor (TFG)β is thought to contribute to this process.

9 Virtually all cognitive tasks that require effortful

processing are thought to require working memory. There are a range of models of working memory,10,11 but most are variants of the Baddeley model.9 Regardless of the view one adopts, there is no question that working memory declines with age, particularly the processing or central executive component, as evidenced by the data presented in Figure 1.12,13 Hasher and Zacks14 have emphasized the Inhibitors,research,lifescience,medical role of inhibition, rather than working memory, in age-related cognitive declines. They proposed that older adults are less effective at inhibiting irrelevant information than young adults. They argue that working memory capacity is not limited with age, but rather is filled with “mental clutter” so that capacity appears to be diminished. Older adults are assumed to be particularly deficient Inhibitors,research,lifescience,medical in a deletion operation in working memory whereby irrelevant information is efficiently discarded when it is no longer needed. There is considerable evidence that older adults have difficulty inhibiting irrelevant information in working memory.15-18 There is Inhibitors,research,lifescience,medical also evidence that older adults have difficulty in flexibly deploying mental resources and/or switching among different tasks. Two good everyday examples

that require task switching are day-trading stocks and piloting an airplane. Both the day trader and airline pilot must constantly shift attention among various indicators and adjust their behavior accordingly (eg, trade a stock or adjust altitude). There is considerable evidence that older Inhibitors,research,lifescience,medical adults have difficulty

switching from one operation to another AZD8055 mouse relative to young adults,19-21 with older adults showing larger time costs for switching between tasks (or metaphorically, reloading mental software) than young adults, Inhibitors,research,lifescience,medical when compared with receiving repeated trials on the same task. Another process that is important for many cognitive tasks, but particularly long-term memory tasks, is the ability to connect a memory event to a context. For example, an older adult may remember that he was told to take shark cartilage to improve his/her arthritis. What the older adult may not remember is whether they were instructed Rolziracetam to do this by a personal physician or were told to do this by a friend who had just read it in the popular press. Thus, the older adult may find they remember a fact, but not the source of the information.22,23 This decreased ability to bind target information to source or context is a problem for older adults in long-term memory tasks24-26 as well as working memory.15 Finally, there is no question that long-term memory declines with age (Figure 1). Problems with decreases in speed, working memory, switching, inhibition, and binding could all contribute to poor long-term memory.

The neoplastic cells show an extremely high proliferation index with nearly 100% of tumor cells showing nuclear accentuation by Ki-67 (45). Molecular abnormalities As previously mentioned, all three subtypes of BL typically demonstrate any of three c-MYC translocations at band 8q24; the most common of which is with immunoglobulin heavy (IgH) chain gene at 14q32, and infrequently with Ig kappa (IgK) at 2p12 or Ig lambda (IgL) at 22q11. However, c-MYC rearrangement is not specific for BL. Approximately 28-50% of GI tract, de novo DLBCLs, and DLBCL, unclassifiable, with features intermediate Inhibitors,research,lifescience,medical between

DLBCL and BL (DLBCL/BL) show c-MYC translocation with a non-Ig gene partner, complex karyotype, and simultaneous BCL2, BCL6 and/or PAX5 translocations, referred to as “double or triple hit” lymphoma (43). Morphological overlap exists between BL and high-grade Inhibitors,research,lifescience,medical DLBCL and/or DLBCL/BL; therefore, it is imperative to differentiate BL from DLBCL

and DLBCL/BL, particularly since the latter two entities are more resistant to chemotherapy Inhibitors,research,lifescience,medical and carry a poorer prognosis overall (43). Prognosis BL is chemosensitive and the advent of high intensity, multi-agent chemotherapeutic regimen has led to an astoundingly high remission rate. As observed in one case, patients with concomitant H. pylori infection may also benefit from H. pylori eradication treatment (45). Epstein-Barr virus positive diffuse large B-cell lymphoma (EBV-positive DLBCL) of the elderly EBV-positive Inhibitors,research,lifescience,medical DLBCL is a clonal B-cell neoplasm in patients older than 50 years without known immunodeficiency or prior lymphoma (48,49). About 70% of these patients present with extranodal EBV-positive B-cell lymphomas in a number of locations, including the stomach in approximately 9% of cases (48). Pathogenesis EBV-positive DLBCL is believed to arise in the context of declining immunity related to senescence Inhibitors,research,lifescience,medical (48-50). As with

other variants of DLBCL, a clear etiology is not yet known. Morphology and immunophenotype Age-related EBV-positive lymphomas generally show large lymphoid cells in a selleck inhibitor background of smaller, reactive components (small lymphocytes, plasma cells, histiocytes, and epithelioid cells). There may also be patchy necrosis and a relatively broad range of B cell maturation, including morphologic centroblasts, immunoblasts, very and Hodgkin Reed Sternberg-like (HRS-like) giant cells with distinct nucleoli (49). This variability distinguishes the disease into two subtypes: large-cell and polymorphic. Large cell lymphoma is characterized by relatively monomorphic large lymphoid cells, while polymorphic lymphoma shows scattered large cells in a polymorphous background consisting of smaller lymphocytes, plasma cells, and histiocytes.