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1.  Gallbladder agenesis with choledochal cyst—a rare association: a case report and review of possible genetic or embryological links 
BMJ Case Reports  2013;2013:bcr2012006786.
Gallbladder agenesis is a rare congenital anomaly. Choledochal cysts are uncommon. The combination of both these entities in a 56-year-old woman is reported. A previously fit and well woman, presented to the emergency department with a 3-day history of abdominal pain. Preoperative imaging and intraoperative findings confirmed gallbladder agenesis and a type I choledochal cyst. There were no other anomalies. She underwent a resection of the choledochal cyst and reconstruction by hepaticojejunostomy.
PMCID: PMC3604316  PMID: 23307450
2.  Liquefaction of Semen Generates and Later Degrades a Conserved Semenogelin Peptide That Enhances HIV Infection 
Journal of Virology  2014;88(13):7221-7234.
Semen enhances HIV infection in vitro, but how long it retains this activity has not been carefully examined. Immediately postejaculation, semen exists as a semisolid coagulum, which then converts to a more liquid form in a process termed liquefaction. We demonstrate that early during liquefaction, semen exhibits maximal HIV-enhancing activity that gradually declines upon further incubation. The decline in HIV-enhancing activity parallels the degradation of peptide fragments derived from the semenogelins (SEMs), the major components of the coagulum that are cleaved in a site-specific and progressive manner upon initiation of liquefaction. Because amyloid fibrils generated from SEM fragments were recently demonstrated to enhance HIV infection, we set out to determine whether any of the liquefaction-generated SEM fragments associate with the presence of HIV-enhancing activity. We identify SEM1 from amino acids 86 to 107 [SEM1(86-107)] to be a short, cationic, amyloidogenic SEM peptide that is generated early in the process of liquefaction but that, conversely, is lost during prolonged liquefaction due to the activity of serine proteases. Synthetic SEM1(86-107) amyloids directly bind HIV-1 virions and are sufficient to enhance HIV infection of permissive cells. Furthermore, endogenous seminal levels of SEM1(86-107) correlate with donor-dependent variations in viral enhancement activity, and antibodies generated against SEM1(86-107) recognize endogenous amyloids in human semen. The amyloidogenic potential of SEM1(86-107) and its virus-enhancing properties are conserved among great apes, suggesting an evolutionarily conserved function. These studies identify SEM1(86-107) to be a key, HIV-enhancing amyloid species in human semen and underscore the dynamic nature of semen's HIV-enhancing activity.
IMPORTANCE Semen, the most common vehicle for HIV transmission, enhances HIV infection in vitro, but how long it retains this activity has not been investigated. Semen naturally undergoes physiological changes over time, whereby it converts from a gel-like consistency to a more liquid form. This process, termed liquefaction, is characterized at the molecular level by site-specific and progressive cleavage of SEMs, the major components of the coagulum, by seminal proteases. We demonstrate that the HIV-enhancing activity of semen gradually decreases over the course of extended liquefaction and identify a naturally occurring semenogelin-derived fragment, SEM1(86-107), whose levels correlate with virus-enhancing activity over the course of liquefaction. SEM1(86-107) amyloids are naturally present in semen, and synthetic SEM1(86-107) fibrils bind virions and are sufficient to enhance HIV infection. Therefore, by characterizing dynamic changes in the HIV-enhancing activity of semen during extended liquefaction, we identified SEM1(86-107) to be a key virus-enhancing component of human semen.
PMCID: PMC4054457  PMID: 24741080
3.  6-Thioguanine and zebularine down-regulate DNMT1 and globally demethylate canine malignant lymphoid cells 
BMC Veterinary Research  2014;10(1):290.
The antimetabolite 6-thioguanine (6-TG) has been used to treat both human and canine lymphoid malignancies. 6-TG has been shown to be epigenetically active as a demethylating agent in a human lymphoma cell line, causing downregulation of DNA methyltransferase 1 (DNMT1) through ubiquitin-targeted degradation. Zebularine (Zeb), a similar cytidine analog, also has demethylating activity as well as oral bioavailability. The hypothesis of the present study was that 6-TG and Zeb would cause downregulation of DNMT1 and globally demethylate the genomic DNA of canine lymphoma cells. The secondary hypothesis was that these agents would cause a dose-dependent decrease in cell proliferation in canine lymphoma cells. Canine CLGL-90 malignant T cells and CLL 17–7 cells were incubated in modified RPMI media. They were treated with 6-TG, Zeb, or control media at biologically relevant concentrations.
Following treatment with each agent, DNMT1 protein and global DNA methylation were significantly decreased. A dose-dependent decrease in cell survival was also observed, with apoptosis being the primary mode of cell death in the CLGL-90 cell line.
These results confirm the demethylating action of 6-TG and Zeb in canine cells which is similar to that shown in human cell lines. Confirmation of this mechanism supports the clinical application of these compounds as demethylating drugs in veterinary patients.
PMCID: PMC4272768  PMID: 25480665
Lymphoma; Demethylation; Thioguanine; DNMT; Canine
4.  Parry-Romberg Syndrome: A Case of Late Onset with Rapid Progression 
Parry–Romberg syndrome (PRS) or progressive hemifacial atrophy is rare, poorly understood condition with an unclear aetiology and characterized by slow and progressive atrophy affecting one side of the face. PRS is a syndrome with diverse presentation and the most common early sign is a painless cleft, the “coup de sabre” near the midline of the face which marks the boundary between the normal and atrophic tissues. Characteristically, the atrophy starts in the first decade of life and progresses slowly for several years before it becomes quiescent. This article describes a case of PRS in a 19-year-old female patient affecting the right side of the face which is unique in the fact that it had a late onset with rapid progression.
PMCID: PMC4225993  PMID: 25386541
Facial hemiatrophy; Parry-romberg syndrome; Progressive hemifacial atrophy
5.  The health effects of fetal microchimerism can be modeled in companion dogs 
Chimerism  2013;4(4):139-141.
Fetal microchimerism (FMC) has been described to have a range of effects on health and disease. Y-chromosomal DNA has been detected in Golden Retrievers suggesting persistent FMC. In that report, nine dogs had evidence of microchimerism without prior pregnancy. To further understand this finding, a dam with prior male live births giving birth to her fourth litter of puppies, all females, was evaluated for FMC along with two of her daughters. All three female dogs had evidence of Y-chromosomal DNA in their blood. This suggests that male cells carried by the dam from previous pregnancy trafficked to her daughters to establish microchimerism in younger siblings. Companion dogs share many of the same cancers as humans, have out-bred genetics, and share the human environment, making them optimal models of human disease. Understanding the impact of FMC on health and disease of dogs could elucidate mechanisms useful for clinical interventions in humans.
PMCID: PMC3921196  PMID: 24080551
Fetal microchimerism; dogs; cancer; sibling microchimerism; immunology
6.  Expression of VEGF in Periodontal Tissues of Type II Diabetes Mellitus Patients with Chronic Periodontitis -an Immunohistochemical Study 
Background: Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability, but information about its role in periodontal diseases is limited. The aim of this study is to determine the association between VEGF expression in healthy and periodontally diseased tissues of healthy and diabetic patients.
Materials and Methods: Seventeen systemically healthy and 17 Type 2 diabetic patients (DM), all diagnosed with periodontitis were enrolled into the study. Gingival samples were collected from both periodontal and healthy sites in all patients. Each patient served as his/her own control samples were subjected to immunohistochemical analysis.
Results: The diseased sites of diabetic subjects expressed higher level of VEGF when compared to diseased sites of non diabetic subjects with chronic periodontitis, VEGF was observed in healthy periodontal tissues of both diabetic and systemically healthy people with periodontitis and VEGF was intensely present in monocytes and macrophages.
Conclusion: The increased expression of VEGF in diseased sites of diabetic patients suggests that diabetes mellitus might have direct influence over VEGF expression.
PMCID: PMC4190781  PMID: 25302255
Diabetes mellitus; Heat induced enzyme retrievel; Vascular endothelial growth factor
7.  Intraosseous Myoepithelial Carcinoma of Mandible- A Case Report with Clinical, Radiological, Histopathologic and Immuno-Histochemical Features 
The primary central salivary gland neoplasms of the mandible are rare. They look clinically and radiographically similar to the odontogenic tumours or cysts which are common in the mandible. Myoepithelial carcinoma is a malignant counter part of myoepithelioma. Their diagnosis mainly depends only on thorough histopathological examination. This paper is to report a case of extra salivary tumour, intraosseous myoepithelial carcinoma of right ramus of the mandible. This case report serves to increase awareness and improve the index of diagnosis.
PMCID: PMC4190812  PMID: 25302285
F- Primary central myoepithelial carcinoma; Intraosseous malignant myoepithelioma; Malignant salivary gland carcinoma of mandible
8.  Factors predicting poor outcome in patients with fulminant Guillaine-Barré syndrome 
This paper describes three patients with acute fulminant Guillain-Barrι Syndrome (GBS) with electrophysiologically inexcitable peripheral nerves not responding to two courses of intravenous immunoglobulin. Their clinical profile is compared with two other GBS patients having similar severity of disease but with demyelinative features, managed similarly during the same period. Patients who failed to respond were elderly with a mean age of 60 years, had prodromal diarrhea, rapid progression of muscle weakness requiring mechanical ventilation within 24 hours, dense weakness of all four limbs with cardiovascular autonomic symptoms and inexcitable peripheral nerves. The remaining two who recovered well were relatively younger with a mean age of 50 years, had no prodromal diarrhea, required ventilatory support by fourth day of illness, no cardiovascular autonomic symptoms and demyelinative neuropathy.
PMCID: PMC4251027  PMID: 25506175
Guillain-Barré Syndrome (GBS); inexcitable nerves; intravenous immunoglobulin (IVIG)
9.  Bacterial Quorum Sensing Molecule N-3-Oxo-Dodecanoyl-L-Homoserine Lactone Causes Direct Cytotoxicity and Reduced Cell Motility in Human Pancreatic Carcinoma Cells 
PLoS ONE  2014;9(9):e106480.
In spite of chemotherapeutic and surgical advances, pancreatic cancer continues to have a dismal prognosis. Metastasis due to tumor cell migration remains the most critical challenge in treating pancreatic cancer, and conventional chemotherapy is rarely curative. In the quest for more novel molecules to fight this disease, we tested the hypothesis that the Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxo-dodecanoyl-L-homoserine lactone (O-DDHSL) would be cytotoxic to and reduce mobility of pancreatic carcinoma cells (Panc-1 and Aspc-1). Results showed a decrease in cell viability from apoptosis, diminished colony formation, and inhibition of migration of the evaluated pancreatic carcinoma cell lines. Also, cell viability decreased in the presence of O-DDHSL when cells were grown in matrigel basement membrane matrix. While messenger RNA for IQGAP-1 decreased in Panc-1 and HPDE cells upon exposure to O-DDHSL, no change was observed in Aspc-1 cells. Cofilin mRNA expression was found to be increased in both HPDE and Panc-1 cells with marginal decrease in Aspc-1 cells. RhoC, a Rho-family GTPase involved in cell motility, increased in the presence of O-DDHSL, suggesting a possible compensatory response to alteration in other migration associated genes. Our results indicate that O-DDHSL could be an effective biomolecule in eukaryotic systems with multimodal function for essential molecular targeting in pancreatic cancer.
PMCID: PMC4154711  PMID: 25188245
12.  Parasystole in a Mahaim Accessory Pathway 
Automaticity has been described in Mahaim pathways, both spontaneously and during radiofrequency ablation. We describe an unusual case of automatic rhythm from a Mahaim pathway presenting as parasystole. The parasystolic beats were also found to initiate tachycardia, resulting in initial presentation with incessant tachycardia and tachycardia induced cardiomyopathy.
PMCID: PMC4100083  PMID: 25057225
Mahaim tachycardia; Parasystole; Automaticity
13.  Normal sensory and range of motion (ROM) responses during Thoracic Slump Test (ST) in asymptomatic subjects 
The purpose of the study was to determine the normal sensory and range of motion (ROM) responses during the movement components of Thoracic Slump Test (Thoracic ST) in asymptomatic subjects. Sixty asymptomatic subjects were included in the study. Thoracic ST was performed in two sequences, proximal initiation, which was proximal to distal and distal initiation, which was distal to proximal. Subjects were randomized into four groups depending on the order of sequences and sides. Outcome measures of sensory responses (intensity, type, and location) and ROM responses were recorded after each sequence. Friedman’s test was done to compare between sensory responses of the subjects. Between-component comparison for prevalence of sensory responses within each sequence was done using Kruskal–Wallis test and Wilcoxonsigned ranks test was used for between-component comparisons of intensity of symptoms within each sequence of testing. Independent t test was used to assess the ROM responses. Results show the prevalence of sensory responses, its nature, area and intensity. These sensory and ROM responses may be considered as normal response of Thoracic ST. The intensity of the symptoms of proximal initiation sequence (1.09±1.35 cm) was significant (P<0.05) when compared to distal initiation sequence (0.08±1.26 cm). The change in the ROM was significant (P<0.05) for distal initiation (7.55±4.51 degrees) when compared to proximal initiation (4.96±3.76 degrees). These normal responses may be used as a reference when using the Thoracic ST as an assessment technique.
PMCID: PMC3578192  PMID: 24421610
Spine; Thoracic Sympathetic slump; Mobilization; Normal response; Neurodynamics
15.  Immediate implants in anterior maxillary arch 
The aim of the study was to evaluate the osseo-integration and soft tissue status of the endosseous implants placed in immediate extraction socket.
Seven patients (4 males and 3 females) aged 20-30 years were selected for the study. Nine implants were placed in seven patients in the maxillary arch. All the patients were clinically αnd thoroughly examined. Under local anesthesia, the indicated tooth was extracted. The extracted socket was prepared using standard drills with palatal wall as guide. The longest and widest implants were placed (Hi-Tec Implants). All implants showed good primary stability. The implants used in the study were tapered design endosseous implants with Threaded implants (TI) unit plasma-sprayed surface. Surgical re-entry (secondary surgery) was performed to remove the healing cap after 6 months for supra crestal fabrication. All patients were reviewed periodically at 3rd and 6th month interval and the following clinical parameters including modified plaque index (mPlI), modified bleeding index (mBI), probing depth (PD), attachment level (AL), and distance between the implant shoulder and mucosal margin (DIM), distance between the implant shoulder and first bone-implant contact, and Clinical Mobility Index were recorded. The results were computed and subjected to statistical evaluation.
The mPlI, mBI, PD, AL, and DIM were evaluated around the implants at baseline, 3rd and 6th month intervals and analyzed statistically by Friedman T-test. The results of the above were shown to be statistically non-significant. The distance between the implant shoulder and first bone implant contact was evaluated around the implants at base line, 3rd and 6th month intervals. The results proved to be statistically significant (0.01) implying that there was a bone apposition around the implants.
During the course of the study, soft tissue status around implants was found to be healthy. Osseointegration as assessed by clinical and radiographic findings was found to be sound.
PMCID: PMC3961959  PMID: 24678203
Bone borne implants; dental implants; endosseous implants; immediate implants; osseointegration
16.  An Exploratory Analysis of Levels of Evidence for Articles Published in Indian Journal of Palliative Care in the years 2010-2011 
Indian Journal of Palliative Care  2013;19(3):170-179.
Indian Journal of Palliative Care (IJPC) provides a comprehensive multidisciplinary evidence base for an evidence-informed clinical decision making.
To analyze the levels of evidence of articles published in IJPC in the years 2010-2011.
Settings and Design:
Systematic review of palliative care journals.
Materials and Methods:
Systematic review of articles was done and was scored according to Center for Evidence-Based Medicine levels of evidence into any of the five grades. The articles were categorized based upon article type, number of authors, study approach, age focus, population focus, disease focus, goals of care, domains of care, models of care, and year of publication.
Statistical Analysis Used:
All descriptive analysis was done using frequencies and percentiles, and association between all categorical variables was done using Chi-square test at 95% confidence interval (CI) using Statistical Package for Social Sciences (SPSS) version 16 for Windows (SPSS Inc, Chicago, IL).
There was a greater prevalence of low level evidence (level 4: n = 46, 51%; level 5: n = 35, 39%) among the 90 selected articles, and article type (original articles with higher level of evidence, P = 0.000), article approach (analytical studies with higher level of evidence, P = 0.000), domains of palliative care (practice-related studies with higher level of evidence, P = 0.000) and models of care (biological or psychosocial model with higher level of evidence, P = 0.044) had a significant association with the grade of levels of evidence. Association with other factors was not statistically significant (P < 0.05).
The levels of research evidence for palliative care provided by articles published in IJPC were predominantly level 4 and level 5, and there is scope for more high quality evidence to inform palliative care decisions in the developing countries.
PMCID: PMC3853396  PMID: 24347908
Evidence analysis; Evidence-based palliative care; Evidence hierarchy; Journal analysis; Levels of evidence
20.  Y-chromosome DNA Is Present in the Blood of Female Dogs Suggesting the Presence of Fetal Microchimerism 
PLoS ONE  2013;8(7):e68114.
Fetal microchimerism has been suggested to play contradictory roles in women’s health, with factors including age of the recipient, time elapsed since microchimerism occurred, and microchimeric cell type modulating disease. Both beneficial and harmful effects have been identified in wound healing and tissue regeneration, immune mediated disease, and cancer. This area of research is relatively new, and hindered by the time course from occurrence of fetal microchimerism to the multi-factorial development of disease. Dogs represent an excellent model for study of fetal microchimerism, as they share our environment, have a naturally condensed lifespan, and spontaneously develop immune-mediated diseases and cancers similar to their human counterparts. However, fetal microchimerism has not been described in dogs. These experiments sought preliminary evidence that dogs develop fetal microchimerism following pregnancy. We hypothesized that Y chromosomal DNA would be detected in the peripheral blood mononuclear cells of female dogs collected within two months of parturition. We further hypothesized that Y chromosomal DNA would be detected in banked whole blood DNA samples from parous female Golden Retrievers with at least one male puppy in a prior litter. Amplification of DNA extracted from five female Golden Retrievers that had whelped within the two months prior to collection revealed strong positive bands for the Y chromosome. Of banked, parous samples, 36% yielded positive bands for the Y chromosome. This is the first report of persistent Y chromosomal DNA in post-partum female dogs and these results suggest that fetal microchimerism occurs in the canine species. Evaluation of the contributions of fetal microchimeric cells to disease processes in dogs as a model for human disease is warranted.
PMCID: PMC3704588  PMID: 23861856
21.  Palatal pyogenic granulomaa 
Journal of Pharmacy & Bioallied Sciences  2013;5(Suppl 2):S179-S181.
Pyogenic granuloma (PG) is a kind of inflammatory hyperplasia seen in the oral cavity. This term is a misnomer because the lesion is unrelated to infection. In reality it arises in response to various stimuli such as low-grade local irritation, traumatic injury or hormonal factors. It predominantly occurs in the second decade of life in young females possibly because of the vascular effects of female hormones. It is also called as pregnancy tumor because of its high frequency of occurrence during the early part of pregnancy. Even though, this lesion is non-neoplastic and treatment procedure is simple, it should be diagnosed correctly before proceeding with the treatment. The most common site for PGs is gingiva (75%) and rarely in the palate. In this case report, we are going to present very rare occurrence of pregnancy tumor in the hard palate.
PMCID: PMC3740672  PMID: 23956603
Inflammatory hyperplasia; oral cavity; pregnancy tumor; pyogenic granuloma
22.  Hypodontia and hypoplasia of mandible: A rare defect caused by combination therapy  
Journal of Pharmacy & Bioallied Sciences  2013;5(Suppl 2):S182-S184.
Hypodontia is defined as the developmental absence of one or more tooth and it can present in varying degrees of severity and severe hypodontia has been defined as the absence of six teeth, excluding third molars. Radiation plays an important role in the treatment of head and neck cancer, in spite of its benefits, radiation has several side-effects in the head and neck region. This article highlights a case report, where hypodontia, hypoplasia of mandible, stunded permanent teeth roots, microdontia, inversion of tooth bud were observed in 19 years old patient who was diagnosed with Langerhans cell histiocytosis at her age of 3 years she had received a combination of radiotherapy and chemotherapy for a period of 1 year and radiation of 50 Gy was used in the head and neck region. Radiographs were taken and it revealed abnormal changes in growth and development of bone and teeth.
PMCID: PMC3740673  PMID: 23956604
Chemotherapy; langerhans cell histiocytosis radiotherapy; hypodontia; hypoplasia of mandible
25.  Mechanism-based Classification and Physical Therapy Management of Persons with Cancer Pain: A Prospective Case Series 
Mechanism-based classification (MBC) was established with current evidence and physical therapy (PT) management methods for both cancer and for noncancer pain.
This study aims to describe the efficacy of MBC-based PT in persons with primary complaints of cancer pain.
Settings and Design:
A prospective case series of patients who attended the physiotherapy department of a multispecialty university-affiliated teaching hospital.
Material and Methods:
A total of 24 adults (18 female, 6 male) aged 47.5 ± 10.6 years, with primary diagnosis of heterogeneous group of cancer, chief complaints of chronic disabling pain were included in the study on their consent for participation The patients were evaluated and classified on the basis of five predominant mechanisms for pain. Physical therapy interventions were recommended based on mechanisms identified and home program was prescribed with a patient log to ensure compliance. Treatments were given in five consecutive weekly sessions for five weeks each of 30 min duration.
Statistical Analysis Used:
Pre–post comparisons for pain severity (PS) and pain interference (PI) subscales of Brief pain inventory-Cancer pain (BPI-CP) and, European organization for research and treatment in cancer-quality of life questionnaire (EORTC-QLQ-C30) were done using Wilcoxon signed-rank test at 95% confidence interval using SPSS for Windows version 16.0 (SPSS Inc, Chicago, IL).
There were statistically significant (P < 0.05) reduction in pain severity, pain interference and total BPI-CP scores, and the EORTC-QLQ-C30.
MBC-PT was effective for improving BPI-CP and EORTC-QLQ-C30 scores in people with cancer pain.
PMCID: PMC3680836  PMID: 23766592
Cancer pain; Pain mechanisms; Palliative care; Physical therapy

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