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Background: The impact of intraoperative starch-based fluid therapy on postoperative kidney dysfunction in patients undergoing major abdominal surgery is uncertain. Low molecular weight starch is expected to cause less postoperative kidney dysfunction., Methods: This retrospective study evaluated the impact of intraoperative 6% hydroxyethyl starch on postoperative renal dysfunction. The primary outcome of this study was postoperative acute kidney injury as per KDIGO definition within 72 hours of surgery., Results: This study analysed data from 461 patients with a median (interquartile range) age of 45 (33-58) years, and 48.2% of all patients were female. The proportion (95% confidence interval) of patients who developed acute kidney injury was 0.18 (0.14-0.21); 62.9% of patients had acute kidney injury stage I, 32% had acute kidney injury stage II, and the rest were acute kidney injury stage III. In the propensity score-matched sample, the average treatment effect of intraoperative colloid use on postoperative serum creatinine at day 3 (p = 0.32), duration of postoperative intensive care unit stay (p = 0.97), duration of hospital stay (p = 0.37), postoperative worst international normalised ratio (p = 0.92), and postoperative transfusion requirement (p = 0.40) were not statistically significant., Conclusion: Intraoperative use of low molecular weight hydroxyethyl starch use was not associated with postoperative kidney dysfunction and coagulopathy in adult patients undergoing major open abdominal surgery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Multiple sclerosis is an inflammatory, autoimmune demyelinating condition and poses diagnostic challenges due to varied presentations. This case report presents a divergence from typical clinical presentations of multiple sclerosis (MS), as the initial presentation resembled symptoms of a brain stem stroke. Conventionally, MS suspicion arises in the presence of previous neurological deficits or signs of optic neuritis. This case emphasises the need for high suspicion of MS in a suspected stroke or transient ischaemic attack (TIA). A 29-year-old woman presented with symptoms characterised by crossed hemiparesis, reduced coarse touch sensation, and paraesthesia of face and upper limb, which initially mimicked symptoms of a brain stem stroke with a normal CT head. MRI revealed multiple hyperintense lesions indicative of demyelinating disease, likely MS. MRI contrast did not identify active lesions. Further investigations included a vasculitis screen, MOG antibodies, and serum angiotensin-converting enzyme (ACE) levels. Treatment with intravenous methylprednisolone for working diagnosis of clinically isolated syndrome (CIS), a classification subset of MS, resulted in symptomatic improvement. The patient responded well and had a lumbar puncture in neurology follow-up, confirming relapsing and remitting multiple sclerosis (RRMS) and was started on disease-modifying treatment (DMT). Diagnosis of MS relies on McDonald criteria, emphasising dissemination in time and space. Early intervention and familiarity with diagnostic criteria are crucial when dealing with MS. This case highlights the diagnostic complexities of MS and the importance of a comprehensive approach to clinical evaluation. A young patient presenting with progressive symptoms affecting activities of daily living should prompt urgent investigations for early initiation of treatment. Familiarity with diagnostic criteria and treatment options optimises patient care in MS management., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Karri et al.)

Polycythemia vera is an indolent myeloproliferative disorder that predisposes patients to venous and arterial thrombosis and can transform into myelofibrosis and acute myeloid leukemia. Consistent phlebotomy prevents life-threatening cerebrovascular and coronary artery disease and prolongs survival in low-risk polycythemia vera (patients under 60 years without thrombosis). However, despite its effectiveness in preventing serious complications, phlebotomy does not necessarily enhance the quality of life (QoL). This review assesses QoL issues associated with low-risk PV, explores alternative management strategies such as erythrocytapheresis, and discusses the roles of hydroxyurea, peginterferon, ruxolitinib, and other novel agents in potentially improving disease management and patient outcomes.

Background and Aims: Magnesium sulfate (MgSO 4 ) has been demonstrated to have analgesic property in various clinical settings. This study explores if addition of MgSO 4 to ropivacaine increases its analgesic efficacy when infiltrated continuously in the postsurgical wound following total abdominal hysterectomy., Material and Methods: This randomized controlled trial was conducted at a tertiary care referral hospital in New Delhi, India. Fifty-two patients were randomized into two groups to receive the intervention of which 48 were able to complete the study. The first group ( n = 26) received 0.25% ropivacaine infiltration and the second group ( n = 26) received 0.25% ropivacaine with 5% MgSO 4 at the incision site for 48 h postoperatively. Primary objective was to compare the total postoperative opioid (morphine) consumption by the study participants in both the groups and the secondary objectives were pain scores at rest and at movement, patient satisfaction score, and wound quality of life on the 7 th postoperative day among the two groups., Results: Both the groups were comparable in their demographic characteristics. The median morphine consumed at 48 h postoperatively was 16.5 [0-77] mg in the ropivacaine group and 13[1-45] mg in the ropivacaine with MgSO 4 group and the difference was statistically insignificant ( P = 0.788). There was no statistical difference between the groups with respect to the pain scores, patient satisfaction, or wound quality of life at 7 days., Conclusion: The addition of MgSO 4 to ropivacaine does not confer any additional postoperative analgesic benefits over ropivacaine alone in continuous wound infiltration following total abdominal hysterectomy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Anaesthesiology Clinical Pharmacology.)

Objectives: To identify and validate novel COVID-19 subphenotypes with potential heterogenous treatment effects (HTEs) using electronic health record (EHR) data and 33 unique biomarkers., Design: Retrospective cohort study of adults presenting for acute care, with analysis of biomarkers from residual blood collected during routine clinical care. Latent profile analysis (LPA) of biomarker and EHR data identified subphenotypes of COVID-19 inpatients, which were validated using a separate cohort of patients. HTE for glucocorticoid use among subphenotypes was evaluated using both an adjusted logistic regression model and propensity matching analysis for in-hospital mortality., Setting: Emergency departments from four medical centers., Patients: Patients diagnosed with COVID-19 based on International Classification of Diseases , 10th Revision codes and laboratory test results., Interventions: None., Measurements and Main Results: Biomarker levels generally paralleled illness severity, with higher levels among more severely ill patients. LPA of 522 COVID-19 inpatients from three sites identified two profiles: profile 1 ( n = 332), with higher levels of albumin and bicarbonate, and profile 2 ( n = 190), with higher inflammatory markers. Profile 2 patients had higher median length of stay (7.4 vs 4.1 d; p < 0.001) and in-hospital mortality compared with profile 1 patients (25.8% vs 4.8%; p < 0.001). These were validated in a separate, single-site cohort ( n = 192), which demonstrated similar outcome differences. HTE was observed ( p = 0.03), with glucocorticoid treatment associated with increased mortality for profile 1 patients (odds ratio = 4.54)., Conclusions: In this multicenter study combining EHR data with research biomarker analysis of patients with COVID-19, we identified novel profiles with divergent clinical outcomes and differential treatment responses., Competing Interests: Drs. Verhoef, Lopez-Espina, Reddy, and Sinha received support for article research from the National Institutes of Health (NIH). Drs. Spicer and Churpek disclosed grant funding from NIH/National Institute of General Medical Sciences, R01 GM123193; Department of Defense/Peer-reviewed medical research program, W81XWH-21-1-0009l; and NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), R01-DK126933-A1. Drs. Lopez-Espina’s and Reddy’s institutions received funding from the NIH. Drs. Lopez-Espina, Bhargava, Schmalz, and Reddy disclosed they are employees of Presnosis. Dr. Sims’s institution received funding from Prenosis. Dr. Churpek’s institution received funding from National Heart, Lung, and Blood Institute R01-HL157262-01, NIH/National Institute on Aging R21 AG068720-01, NIH/National Institute on Drug Abuse R01 DA051464-01, NIH/NIDDK R21DK113420-01A1, and he disclosed there is a patent pending (ARCD. P0535US.P2) for risk stratification algorithms for hospitalized patients. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

During translation, messenger RNAs (mRNAs) are decoded by ribosomes which can stall for various reasons. These include chemical damage, codon composition, starvation, or translation inhibition. Trailing ribosomes can collide with stalled ribosomes, potentially leading to dysfunctional or toxic proteins. Such aberrant proteins can form aggregates and favor diseases, especially neurodegeneration. To prevent this, both eukaryotes and bacteria have evolved different pathways to remove faulty nascent peptides, mRNAs and defective ribosomes from the collided complex. In eukaryotes, ubiquitin ligases play central roles in triggering downstream responses and several complexes have been characterized that split affected ribosomes and facilitate degradation of the various components. As collided ribosomes signal translation stress to affected cells, in eukaryotes additional stress response pathways are triggered when collisions are sensed. These pathways inhibit translation and modulate cell survival and immune responses. Here, we summarize the current state of knowledge about rescue and stress response pathways triggered by ribosome collisions., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Background: Optimum procedural sedation is very essential for conducting non-operating room procedures such as endoscopic retrograde cholangiopancreatography (ERCP). The combination of ketamine and dexmedetomidine (KD) is expected to balance out the undesirable effects of either drug and provide smooth sedation. Together ketamine and propofol (KP) also provide synergistic sedation with stable hemodynamics. This prospective, single-blinded randomized study aimed to compare the effect of both the combinations during ERCP in terms of oxygen desaturation, respiratory depression, hemodynamic parameters, analgesia, recovery time, and ease with which the endoscopist could perform the endoscopy., Methods: This prospective, single-blinded randomized study (CTRI/2019/08/020625) was conducted on 84, ASA (American Society of Anesthesiologists) physical status I or II patients, of age 18-65 years presenting for ERCP in a tertiary care center. They were randomized to receive either KD (n=42) or KP (n=42) combination during ERCP. Mean SPO 2 at the end of the procedure was compared between the groups. Apart from these periprocedural hemodynamic and respiratory parameters, pain scores on arrival in the recovery room (t0), 15 minutes (t15), and 30 minutes (t30), recovery time, and endoscopist's satisfaction as per a Likert's scale were recorded., Results: The mean SpO 2 (SpO 2 recorded every minute during the procedure and averaged over procedure time in minutes) in group KP (97.7 [96.1-98.6]) was significantly lower than group KD (98.5 [98.1-98.8]) (p=0.005). The post-procedure pain scores measured at t0 and t15 were higher in group KP (p<0.001 and p=0.043), and comparable at t30 in both the groups (p=0.711). The time to achieve Modified Aldrete score (MAS) ≥ 9 was significantly more in group KD (p<0.001). The lowest mean arterial pressure and heart rate in group KD were significantly lower than in group KP (p<0.001, p=0.006, respectively). The overall endoscopist satisfaction was better in group KP compared to group KD (p= 0.011)., Conclusions: The combination of ketamine-dexmedetomidine for procedural sedation during ERCP is a safe alternative to ketamine-propofol with a better respiratory profile., Clinical Trial Number and Registry Url: CTRI/2019/08/020625 ( www.ctri.nic.in )., (© 2022. Indian Society of Gastroenterology.)

Adenosine triphosphate (ATP) production and utilization is critically important for animal development. How these processes are regulated in space and time during tissue growth remains largely unclear. We used a FRET-based sensor to dynamically monitor ATP levels across a growing tissue, using the Drosophila larval wing disc. Although steady-state levels of ATP are spatially uniform across the wing pouch, inhibiting oxidative phosphorylation reveals spatial differences in metabolic behavior, whereby signaling centers at compartment boundaries produce more ATP from glycolysis than the rest of the tissue. Genetic perturbations indicate that the conserved Hedgehog signaling pathway can enhance ATP production by glycolysis. Collectively, our work suggests the existence of a homeostatic feedback loop between Hh signaling and glycolysis, advancing our understanding of the connection between conserved developmental patterning genes and ATP production during animal tissue development., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Background and Objective: A large number of studies describing the clinicoepidemiological features of coronavirus disease-2019 (COVID-19) patients are available but very few studies have documented similar features of the deceased. This study was aimed to describe the clinicoepidemiological features and the causes of mortality of COVID-19 deceased patients admitted in a dedicated COVID center in India., Methodology: This was a retrospective study done in adult deceased patients admitted in COVID ICU from April 4 to July 24, 2020. The clinical features, comorbidities, complications, and causes of mortality in these patients were analyzed. Pediatric deceased were analyzed separately., Results: A total of 654 adult patients were admitted in the ICU during the study period and ICU mortality was 37.7% (247/654). Among the adult deceased, 65.9% were males with a median age of 56 years [interquartile range (IQR), 41.5-65] and 94.74% had one or more comorbidities, most common being hypertension (43.3%), diabetes mellitus (34.8%), and chronic kidney disease (20.6%). The most common presenting features in these deceased were fever (75.7%), cough (68.8%), and shortness of breath (67.6%). The mean initial sequential organ failure assessment score was 9.3 ± 4.7 and 24.2% were already intubated at the time of admission. The median duration of hospital stay was 6 days (IQR, 3-11). The most common cause of death was sepsis with multi-organ failure (55.1%) followed by severe acute respiratory distress syndrome (ARDS) (25.5%). All pediatric deceased had comorbid conditions and the most common cause of death in this group was severe ARDS., Conclusion: In this cohort of adult deceased, most were young males with age less than 65 years with one or more comorbidities, hypertension being the most common. Only 5% of the deceased had no comorbidities. Sepsis with multi-organ dysfunction syndrome was the most common cause of death., How to Cite This Article: Aggarwal R, Bhatia R, Kulshrestha K, Soni KD, Viswanath R, Singh AK, et al. Clinicoepidemiological Features and Mortality Analysis of Deceased Patients with COVID-19 in a Tertiary Care Center. Indian J Crit Care Med 2021; 25(6):622-628., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

Tissue organization is often characterized by specific patterns of cell morphology. How such patterns emerge in developing tissues is a fundamental open question. Here, we investigate the emergence of tissue-scale patterns of cell shape and mechanical tissue stress in the Drosophila wing imaginal disc during larval development. Using quantitative analysis of the cellular dynamics, we reveal a pattern of radially oriented cell rearrangements that is coupled to the buildup of tangential cell elongation. Developing a laser ablation method, we map tissue stresses and extract key parameters of tissue mechanics. We present a continuum theory showing that this pattern of cell morphology and tissue stress can arise via self-organization of a mechanical feedback that couples cell polarity to active cell rearrangements. The predictions of this model are supported by knockdown of MyoVI, a component of mechanosensitive feedback. Our work reveals a mechanism for the emergence of cellular patterns in morphogenesis., Competing Interests: ND, MP, KI, JF, RP, SE, FJ No competing interests declared, (© 2021, Dye et al.)

The levels of nuclear protein Lamin A/C are crucial for nuclear mechanotransduction. Lamin A/C levels are known to scale with tissue stiffness and extracellular matrix levels in mesenchymal tissues. But in epithelial tissues, where cells lack a strong interaction with the extracellular matrix, it is unclear how Lamin A/C is regulated. Here, we show in epithelial tissues that Lamin A/C levels scale with apico-basal cell compression, independent of tissue stiffness. Using genetic perturbations in Drosophila epithelial tissues, we show that apico-basal cell compression regulates the levels of Lamin A/C by deforming the nucleus. Further, in mammalian epithelial cells, we show that nuclear deformation regulates Lamin A/C levels by modulating the levels of phosphorylation of Lamin A/C at Serine 22, a target for Lamin A/C degradation. Taken together, our results reveal a mechanism of Lamin A/C regulation which could provide key insights for understanding nuclear mechanotransduction in epithelial tissues.

Changes in cell metabolism and plasma membrane potential have been linked to shifts between tissue growth and differentiation, and to developmental patterning. How such changes mediate these effects is poorly understood. Here, we use the developing wing of Drosophila to investigate the interplay between cell metabolism and a key developmental regulator-the Hedgehog (Hh) signalling pathway. We show that reducing glycolysis both lowers steady-state levels of ATP and stabilizes Smoothened (Smo), the 7-pass transmembrane protein that transduces the Hh signal. As a result, the transcription factor Cubitus interruptus accumulates in its full-length, transcription activating form. We show that glycolysis is required to maintain the plasma membrane potential and that plasma membrane depolarization blocks cellular uptake of N-acylethanolamides-lipoprotein-borne Hh pathway inhibitors required for Smo destabilization. Similarly, pharmacological inhibition of glycolysis in mammalian cells induces ciliary translocation of Smo-a key step in pathway activation-in the absence of Hh. Thus, changes in cell metabolism alter Hh signalling through their effects on plasma membrane potential., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Competing Interests: There are no conflicts of interest.

During morphogenesis, epithelia undergo dynamic rearrangements, which requires continuous remodelling of junctions and cell shape, but at the same time mechanisms preserving cell polarity and tissue integrity. Apico-basal polarity is key for the localisation of the machinery that enables cell shape changes. The evolutionarily conserved Drosophila Crumbs protein is critical for maintaining apico-basal polarity and epithelial integrity. How Crumbs is maintained in a dynamically developing embryo remains largely unknown. Here, we applied quantitative fluorescence techniques to show that, during germ band retraction, Crumbs dynamics correlates with the morphogenetic activity of the epithelium. Genetic and pharmacological perturbations revealed that the mobile pool of Crumbs is fine-tuned by the actomyosin cortex in a stage-dependent manner. Stabilisation of Crumbs at the plasma membrane depends on a proper link to the actomyosin cortex via an intact FERM-domain-binding site in its intracellular domain, loss of which leads to increased junctional tension and higher D E-cadherin (also known as Shotgun) turnover, resulting in impaired junctional rearrangements. These data define Crumbs as a mediator between polarity and junctional regulation to orchestrate epithelial remodelling in response to changes in actomyosin activity.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Studying how epithelia respond to mechanical stresses is key to understanding tissue shape changes during morphogenesis. Here, we study the viscoelastic properties of the Drosophila wing epithelium during pupal morphogenesis by quantifying mechanical stress and cell shape as a function of time. We find a delay of 8 h between maximal tissue stress and maximal cell elongation, indicating a viscoelastic deformation of the tissue. We show that this viscoelastic behavior emerges from the mechanosensitivity of endocytic E-cadherin turnover. The increase in E-cadherin turnover in response to stress is mediated by mechanosensitive relocalization of the E-cadherin binding protein p120-catenin (p120) from cell junctions to cytoplasm. Mechanosensitivity of E-cadherin turnover is lost in p120 mutant wings, where E-cadherin turnover is constitutively high. In this mutant, the relationship between mechanical stress and stress-dependent cell dynamics is altered. Cells in p120 mutant deform and undergo cell rearrangements oriented along the stress axis more rapidly in response to mechanical stress. These changes imply a lower viscosity of wing epithelium. Taken together, our findings reveal that p120-dependent mechanosensitive E-cadherin turnover regulates viscoelastic behavior of epithelial tissues., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Competing Interests: There are no conflicts of interest.

In this article, we summarize current findings for the emergence of biophysical properties such as nuclear stiffness, chromatin compaction, chromosome positioning, and chromosome intermingling during stem cell differentiation, which eventually correlated with the changes of gene expression profiles during cellular differentiation. An overview is first provided to link stem cell differentiation with alterations in nuclear architecture, chromatin compaction, along with nuclear and chromatin dynamics. Further, we highlight the recent biophysical and molecular approaches, imaging methods and computational developments in characterizing transcription-related chromosome organization especially chromosome intermingling and nano-scale chromosomal contacts. Finally, the article ends with an outlook towards the emergence of a functional roadmap in setting up chromosome positioning and intermingling in a cell type specific manner during cellular differentiation., (Copyright © 2017. Published by Elsevier Inc.)

Chromosome territories (CTs) in higher eukaryotes occupy tissue-specific non-random three-dimensional positions in the interphase nucleus. To understand the mechanisms underlying CT organization, we mapped CT position and transcriptional changes in undifferentiated embryonic stem (ES) cells, during early onset of mouse ES cell differentiation and in terminally differentiated NIH3T3 cells. We found chromosome intermingling volume to be a reliable CT surface property, which can be used to define CT organization. Our results show a correlation between the transcriptional activity of chromosomes and heterologous chromosome intermingling volumes during differentiation. Furthermore, these regions were enriched in active RNA polymerase and other histone modifications in the differentiated states. These findings suggest a correlation between the evolution of transcription program in modifying CT architecture in undifferentiated stem cells. This leads to the formation of functional CT surfaces, which then interact to define the three-dimensional CT organization during differentiation., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Physical forces in the form of substrate rigidity or geometrical constraints have been shown to alter gene expression profile and differentiation programs. However, the underlying mechanism of gene regulation by these mechanical cues is largely unknown. In this work, we use micropatterned substrates to alter cellular geometry (shape, aspect ratio, and size) and study the nuclear mechanotransduction to regulate gene expression. Genome-wide transcriptome analysis revealed cell geometry-dependent alterations in actin-related gene expression. Increase in cell size reinforced expression of matrix-related genes, whereas reduced cell-substrate contact resulted in up-regulation of genes involved in cellular homeostasis. We also show that large-scale changes in gene-expression profile mapped onto differential modulation of nuclear morphology, actomyosin contractility and histone acetylation. Interestingly, cytoplasmic-to-nuclear redistribution of histone deacetylase 3 modulated histone acetylation in an actomyosin-dependent manner. In addition, we show that geometric constraints altered the nuclear fraction of myocardin-related transcription factor. These fractions exhibited hindered diffusion time scale within the nucleus, correlated with enhanced serum-response element promoter activity. Furthermore, nuclear accumulation of myocardin-related transcription factor also modulated NF-κB activity. Taken together, our work provides modularity in switching gene-expression patterns by cell geometric constraints via actomyosin contractility.

For cells to adapt to different tissues and changes in tissue mechanics, they must be able to respond to mechanical cues by changing their gene expression patterns. Biochemical signaling pathways for these responses have been elucidated, and recent evidence points to the involvement of force-induced deformation of the nucleus. However, it is still unclear how physical cues received at the plasma membrane (PM) spatiotemporally integrate to the functional chromatin organization of the cell nucleus. To investigate this issue, we applied mechanical forces through magnetic particles adhered to the PM of single cells and mapped the accompanying changes in actin polymerization, nuclear morphology, chromatin remodeling, and nuclear transport of soluble signaling intermediates using high-resolution fluorescence anisotropy imaging. Using this approach, we show the timescales associated with force-induced polymerization of actin and changes in the F/G actin ratio resulting in nuclear translocation of the G-actin-associated transcriptional cofactor, megakaryoblastic acute leukemia factor-1 (MKL). Further, this method of measuring nuclear organization at high spatiotemporal resolution with simultaneous force application revealed the physical propagation of forces to the nucleus, resulting in changes to chromatin organization, followed by nuclear deformation. We also describe a quantitative model that incorporates active stresses and chemical kinetics to evaluate the observed timescales. Our work suggests that mechanical activation of cells is accompanied by distinct timescales involved in the reorganization of actin and chromatin assembly, followed by translocation of transcription cofactors from the cytoplasm to the nucleus., (Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

A study was carried out on 58 healthy volunteers. None of the volunteeres had any foot complaints. This was done to study Indian feet, as foot is an important part of human anatomy and its certain deformities eg, hallux valgus, can be very disabling. We have studied anatomical angles between 1st and 2nd rays of foot eg, angle of hallux valgus and angle of slant of distal facet of medial cuneiform and have shown significant correlation between them and development of hallux valgus. The coefficient of correlation (r) calculated between these two angles is significant, showing that this angle influences the angle of hallux valgus and hence development of hallux valgus. These are anatomical angles and indicate shapes of medial cuneiform and 1st metatarsal. Hence these seem to be inherited, making the feet anatomically predisposed to develop hallux valgus. This view is supported by Gray's Anatomy. The extrinsic factors such as narrow toes, closed, footwear worn for an extended period do increase the angle of hallux valgus. So, in predisposed feet, this is one of the extrinsic factor which can lead to development of hallux valgus. On studying these two angles, orthopaedicians should be on alert and should advise such individuals on wearing foot- friendly foot-wear.

Genomes are spatially assembled into chromosome territories (CT) within the nucleus of living cells. Recent evidences have suggested associations between three-dimensional organization of CTs and the active gene clusters within neighboring CTs. These gene clusters are part of signaling networks sharing similar transcription factor or other downstream transcription machineries. Hence, presence of such gene clusters of active signaling networks in a cell type may regulate the spatial organization of chromosomes in the nucleus. However, given the probabilistic nature of chromosome positions and complex transcription factor networks (TFNs), quantitative methods to establish their correlation is lacking. In this paper, we use chromosome positions and gene expression profiles in interphase fibroblasts and describe methods to capture the correspondence between their spatial position and expression. In addition, numerical simulations designed to incorporate the interacting TFNs, reveal that the chromosome positions are also optimized for the activity of these networks. These methods were validated for specific chromosome pairs mapped in two distinct transcriptional states of T-Cells (naïve and activated). Taken together, our methods highlight the functional coupling between topology of chromosomes and their respective gene expression patterns.

The nucleus is maintained in a prestressed state within eukaryotic cells, stabilized mechanically by chromatin structure and other nuclear components on its inside, and cytoskeletal components on its outside. Nuclear architecture is emerging to be critical to the governance of chromatin assembly, regulation of genome function and cellular homeostasis. Elucidating the prestressed organization of the nucleus is thus important to understand how the nuclear architecture impinges on its function. In this chapter, various chemical and mechanical methods have been described to probe the prestressed organization of the nucleus., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

TSH-secreting tumors comprise less than 2% of all pituitary adenomas. All patients present with hyperthyroidism with a detectable TSH level, and a majority have macroadenomas. Oral cholecystographic agents (e.g. iopanoic acid) potently inhibit the activation of T(4) to the more potent T(3). They have been used successfully to treat primary thyroidal hyperthyroidism and thyroxine overdose. However, they have not been employed in the treatment of central hyperthyroidism. We report, herein, the first two patients with thyrotropinomas, in whom iopanoic acid (Telepaque) has been used perioperatively to safely and rapidly achieve euthyroidism. In case 1, free T(3) index improved from a value of 634 to 175 (normal range 78-162) after 3 d of therapy with iopanoic acid. In case 2, free T(3) by dialysis improved from 697 pg/dl (10.7 pmol/liter) to 195 pg/dl (3.0 pmol/liter) (normal range 210-440 pg/dl; 3.2-6.7 pmol/liter) after 7 d of therapy with iopanoic acid.

We report three patients with imperforate anus and other stigmata of the VATER syndrome who were diagnosed as having tracheoesophageal (TE) fistula, H-type, with intact esophagus. The fistula was diagnosed in two of the three patients only after recurrent respiratory infections.

Fetus in fetu is an extremely rare developmental abnormality secondary to abnormal embryogenesis in a diamniotic monochorionic pregnancy. It occurs when a vertebrate fetus is enclosed within the abdomen of a normally developing fetus. This report describes the prospective diagnosis of fetus in fetu by findings on a plain radiograph and CT scan. At surgery, two fetus in fetu were discovered.

The high level of glucose in blood for a long duration is the main cause of the development of retinopathy. So yearly screening of patients newly diagnosed with NIDDM diabetes is recommended because rare cases of treatable diabetic retinopathy have occurred early in one course of NIDDM diabetes. Hyperglycaemia leads to non-enzymatic glycosylation of proteins and HbA1C was found increased. Antioxidants such as GSH and SOD level is found decreased in retinopathy conditions due to the higher lipid peroxidation, which is evident from high MDA and DC values. So it can be clearly stated that increase in the free radical by hyperglycaemia, lipid peroxidation and advanced glycosylation endproducts along with decreased antioxidants are the causative agents for the development of retinopathy.

An 89-year old patient had mycosis fungoides with extensive skin involvement and palpable but pathologically uninvolved lymph nodes. He was successfully treated with PUVA combined with topical 0.1% fluocinolone acetonide ointment. PUVA therapy is highly effective in the treatment of mycosis fungoides confined to the skin, especially in the elderly where more aggressive therapy may not be tolerated.

The authors present the case of a 12-year-old boy with a history of chronic upper abdominal pain. Based on ultrasonography, endoscopic retrograde cholangio-pancreatography, and computerized tomography, a diagnosis of chronic calcific pancreatitis with dilation of the main pancreatic duct and a pseudocyst of the proximal pancreas was made. At surgery, in addition to confirmation of the above findings, a pseudoaneurysm arising from the splenic artery was found in the head and body of the pancreas. Pancreaticoduodenal resection including the pseudoaneurysm was performed. Postoperatively the child developed diabetes, which is easily managed with small doses of insulin.