INNOVATIONS IN ORTHOPEDIC SURGERY: MINIMALLY INVASIVE TECHNIQUES FOR JOINT REPLACEMENT AND REPAIR.

The scientists compared the outcomes of a minimally invasive operation approach (MIO) to a conventional poster lateral (PL) method in overall hip replacement (OHR) in terms of itchiness, damage to muscles, and bleeding. The factors that researchers examined were the levels of Haemoglobin (Hg), a marker for oxygen depletion, the quantity of Interleukin-6 (IL6), a marker for inflammation, the heart-type fatty acid binding protein (HTFABP), and the health of the muscles. The study's findings showed that IL6 content increased beyond pre-operative levels as a result of the two surgeries. At 6 hours after surgery, the mean IL6 concentration in the PL group was 79.6 pg/ml while in the MIO group it was 76.4 pg/ml. The highest values after 24 hours of therapy were 100 pg/ml in the PL group and 92.3 pg/ml in the MIO category. In each category, IL6 levels had dropped up to this point. The post-operative mean HTFABP concentration in the MIO organization was greater (12.5 mg/l) than in the PL organization (18.3 mg/l) in terms of muscle damage. One day after surgery, however, it reached an apex and began to decline in both groups. The amounts of Hg lost throughout the procedure decreased for both sets. 12.5 g/dl of mercury was present. The MIO grouping had PL 72 hours following a procedure, while the PL grouping had 10.3 g/dl. Between the two surgical methods, there were no obvious differences in bleeding, muscle damage, or edema. These results led the researchers to draw the conclusion that there were little differences between the MIO anterior method and the traditional PL technique in terms of muscle damage, blood loss, or irritability. The lack of a learning curve in the study may account for the lack of alterations seen, they hypothesized, rendering the use of the term "MIO" in describing the approach as less traumatizing dubious. The study's methodology, sample sizes, and all other relevant material were left out, making it impossible to evaluate the study's validity and generalizability in its entirety.

Notch activation by the metalloproteinase ADAM17 regulates myeloproliferation and atopic barrier immunity by suppressing epithelial cytokine synthesis.

Epithelial cells of mucosal tissues provide a barrier against environmental stress, and keratinocytes are key decision makers for immune cell function in the skin. Currently, epithelial signaling networks that instruct barrier immunity remain uncharacterized. Here we have shown that keratinocyte-specific deletion of a disintegrin and metalloproteinase 17 (Adam17) triggers T helper 2 and/or T helper 17 (Th2 and/or Th17) cell-driven atopic dermatitis and myeloproliferative disease. In vivo and in vitro deficiency of ADAM17 dampened Notch signaling, increasing production of the Th2 cell-polarizing cytokine TSLP and myeloid growth factor G-CSF. Ligand-independent Notch activation was identified as a regulator of AP-1 transcriptional activity, with Notch antagonizing c-Fos recruitment to the promoters of Tslp and Csf3 (G-CSF). Further, skin inflammation was rescued and myeloproliferation ameliorated by delivery of active Notch to Adam17(-)(/-) epidermis. Our findings uncover an essential role of ADAM17 in the adult epidermis, demonstrating a gatekeeper function of the ADAM17-Notch-c-Fos triad in barrier immunity.

Planarians as models of cadmium-induced neoplasia provide measurable benchmarks for mechanistic studies.

Bioassays of planarian neoplasia highlight the potential of these organisms as useful standards to assess whether environmental toxins such as cadmium promote tumorigenesis. These studies complement other investigations into the exceptional healing and regeneration of planarians - processes that are driven by a population of active stem cells, or neoblasts, which are likely transformed during planarian tumor growth. Our goal was to determine if planarian tumorigenesis assays are amenable to mechanistic studies of cadmium carcinogenesis. To that end we demonstrate, by examining both counts of cell populations by size, and instances of mitosis, that the activity of the stem cell population can be monitored. We also provide evidence that specific biomodulators can affect the potential of planarian neoplastic growth, in that an inhibitor of metalloproteinases effectively blocked the development of the lesions. From these results, we infer that neoblast activity does respond to cadmium-induced tumor growth, and that metalloproteinases are required for the progression of cancer in the planarian.

Homotypic RANK signaling differentially regulates proliferation, motility and cell survival in osteosarcoma and mammary epithelial cells.

RANKL (receptor activator of NF-κB ligand) is a crucial cytokine for regulating diverse biological systems such as innate immunity, bone homeostasis and mammary gland differentiation, operating through activation of its cognate receptor RANK. In these normal physiological processes, RANKL signals through paracrine and/or heterotypic mechanisms where its expression and function is tightly controlled. Numerous pathologies involve RANKL deregulation, such as bone loss, inflammatory diseases and cancer, and aberrant RANK expression has been reported in bone cancer. Here, we investigated the significance of RANK in tumor cells with a particular emphasis on homotypic signaling. We selected RANK-positive mouse osteosarcoma and RANK-negative preosteoblastic MC3T3-E1 cells and subjected them to loss- and gain-of-RANK function analyses. By examining a spectrum of tumorigenic properties, we demonstrate that RANK homotypic signaling has a negligible effect on cell proliferation, but promotes cell motility and anchorage-independent growth of osteosarcoma cells and preosteoblasts. By contrast, establishment of RANK signaling in non-tumorigenic mammary epithelial NMuMG cells promotes their proliferation and anchorage-independent growth, but not motility. Furthermore, RANK activation initiates multiple signaling pathways beyond its canonical target, NF-κB. Among these, biochemical inhibition reveals that Erk1/2 is dominant and crucial for the promotion of anchorage-independent survival and invasion of osteoblastic cells, as well as the proliferation of mammary epithelial cells. Thus, RANK signaling functionally contributes to key tumorigenic properties through a cell-autonomous homotypic mechanism. These data also identify the likely inherent differences between epithelial and mesenchymal cell responsiveness to RANK activation.

Experimental setup for thermal measurements at the nanoscale using a SThM probe with niobium nitride thermometer.

Scanning Thermal Microscopy (SThM) has become an important measurement technique for characterizing the thermal properties of materials at the nanometer scale. This technique requires a SThM probe that combines an Atomic Force Microscopy (AFM) probe and a very sensitive resistive thermometer; the thermometer being located at the apex of the probe tip allows for the mapping of temperature or thermal properties of nanostructured materials with very high spatial resolution. The high interest of the SThM technique in the field of thermal nanoscience currently suffers from a low temperature sensitivity despite its high spatial resolution. To address this challenge, we developed a high vacuum-based AFM system hosting a highly sensitive niobium nitride (NbN) SThM probe to demonstrate its unique performance. As a proof of concept, we utilized this custom-built system to carry out thermal measurements using the 3ω method. By measuring the V3ω voltage on the NbN resistive thermometer under vacuum conditions, we were able to determine the SThM probe's thermal conductance and thermal time constant. The performance of the probe is demonstrated by performing thermal measurements in-contact with a sapphire sample.

Type A thymoma with generalised myasthenia gravis.

Thymoma is a very rare tumour arising from thymus in the anterior mediastinum. A case of a spindle cell thymoma with Myasthenia gravis in a 34-year-old female who presented with difficulty in breathing and swallowing with shortness of breath is reported.

Exploring fish bioassay of textile dye wastewaters and their selected constituents in terms of mortality and erythrocyte disorders.

Acute (4 day) and short-term (7 day) toxicity studies (at 1/5th and 1/10th of LC(50)) of textile dye wastewaters and their selected ingredients (azo dye methyl red and heavy metals Cd, Cu, Ni and Zn) were made on a freshwater fish Gambusia affinis under laboratory conditions. LC(50) value was found to be the lowest in four cases, and the EC(50) value for reduction in erythrocyte counts in the remaining four tests. Thus, the reduction in erythrocyte counts to the 50% level was similar in sensitivity to fish mortality. The short-term toxicity studies revealed significant disorders in erythrocyte morphology (poikilocytosis) and its counts to be the better indices for toxicity monitoring in the absence of fish mortality.

Unusual presentation of dedifferentiated liposarcoma as paratesticular mass.

A 75-year-old male presented with complaint of painless left inguinoscrotal mass slowly increasing in size since 9 years. Clinical impression was malignancy arising in left testis or cord. Initial incisional biopsy was reported as fibromatosis. Later on wide excision of tumor was done and histopathology showed dedifferentiated liposarcoma with areas of fibromatosis.

Nasal glioma: a case report.

Here we describe a rare case of nasal glioma in a 14 year old boy who presented with history of right nasal obstruction and nasal discharge since 6 months. On examination a pale mass was seen filling the right nasal cavity and extending down in the oropharynx. Clinical impression was antrochoanal polyp. Excision of the mass was carried out and sent for histopathology which showed presence of glial tissue and the diagnosis was made as nasal glioma.

A prospective and retrospective study of actinomycosis in last five years at Manipal Teaching Hospital, Pokhara, Nepal.

OBJECTIVE: The study was carried out to determine the clinical and morphological presentation of actinomycosis and its association with malignancy and other opportunistic infections. MATERIAL AND METHODS: A prospective and retrospective study of cases was done from January 2001 to December 2006 (5 years) in the department of pathology. RESULT: Total 19 cases of actinomycosis were found during this period. Patients presented with discharging sinus and non-healing superficial abscess. Out of 19 cases, three cases were associated with malignancy, two cases were associated with aspergillosis while one case was clinically misdiagnosed as malignancy. All cases were diagnosed pathologically except a case of maxillary sinusitis which was initially suspected as fungal sinusitis by CT scan. Since actinomycosis is often misdiagnosed it is important to know the clinical presentation and morphological features of actinomycosis for correct management. CONCLUSION: The clinical features and histopathological findings of actinomycosis are important to understand for its correct diagnosis and better management of patient.

Antioxidant therapy in the prevention of organ dysfunction syndrome and infectious complications after trauma: early results of a prospective randomized study.

Reactive oxygen species have been implicated in the etiology of multiorgan dysfunction syndrome and infectious complications in trauma patients by either direct cellular toxicity and/or the activation of intracellular signaling pathways. Studies have shown that the antioxidant defenses of the body are decreased in trauma patients; these include glutathione, for which N-acetylcysteine is a precursor, and selenium, which is a cofactor for glutathione. Eighteen trauma patients were prospectively randomized to a control or antioxidant group where they received N-acetylcysteine, selenium, and vitamins C and E for 7 days. As compared with the controls, the antioxidant group showed fewer infectious complications (8 versus 18) and fewer organs dysfunctioning (0 versus 9). There were no deaths in either group. We conclude that these preliminary data may support a role for the use of this antioxidant mixture to decrease the incidence of multiorgan dysfunction syndrome and infectious complications in the severely injured patient. This remains to be confirmed in larger trials.

Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice.

Some cancers have been stratified into subclasses based on their unique involvement of specific signaling pathways. The mapping of human cancer genomes is revealing a vast number of somatic alterations; however, the identification of clinically relevant molecular tumor subclasses and their respective driver genes presents challenges. This information is key to developing more targeted and personalized cancer therapies. Here, we generate a new mouse model of genomically unstable osteosarcoma (OSA) that phenocopies the human disease. Integrative oncogenomics pinpointed cAMP-dependent protein kinase type I, alpha regulatory subunit (Prkar1a) gene deletions at 11qE1 as a recurrent genetic trait for a molecularly distinct subclass of mouse OSA featuring RANKL overexpression. Using mouse genetics, we established that Prkar1a is a bone tumor suppressor gene capable of directing subclass development and driving RANKL overexpression during OSA tumorigenesis. Finally, we uncovered evidence for a PRKAR1A-low subset of human OSA with distinct clinical behavior. Thus, tumor subclasses develop in mice and can potentially provide information toward the molecular stratification of human cancers.

Reye syndrome: a case report with review of literature.

Here we describe a case of Reye syndrome diagnosed at postmortem liver biopsy of a three-year old girl who presented with vomiting, low grade fever for three days and loss of consciousness for 18 hours. Clinically, the differential diagnoses were meningitis, encephalitis and septicemia. No history of past illness or any drug ingestion including aspirin were present. Laboratory investigations indicated a diagnosis of Reye syndrome. The child was given supportive treatment but died after two days of admission and postmortem needle-biopsy of the liver showed microvesicular steatosis consistent with Reye syndrome.

SIRT1 acts as a nutrient-sensitive growth suppressor and its loss is associated with increased AMPK and telomerase activity.

SIRT1, the mammalian homolog of SIR2 in Saccharomyces cerevisiae, is an NAD-dependent deacetylase implicated in regulation of lifespan. By designing effective short hairpin RNAs and a silent shRNA-resistant mutant SIRT1 in a genetically defined system, we show that efficient inhibition of SIRT1 in telomerase-immortalized human cells enhanced cell growth under normal and nutrient limiting conditions. Hematopoietic stem cells obtained from SIRT1-deficient mice also showed increased growth capacity and decreased dependency on growth factors. Consistent with this, SIRT1 inhibition was associated with increased telomerase activity in human cells. We also observed a significant increase in AMPK levels up on SIRT1 inhibition under glucose limiting conditions. Although SIRT1 suppression cooperated with hTERT to promote cell growth, either overexpression or suppression of SIRT1 alone had no effect on life span of human diploid fibroblasts. Our findings challenge certain models and connect nutrient sensing enzymes to the immortalization process. Furthermore, they show that in certain cell lineages, SIRT1 can act as a growth suppressor gene.

Primary malignant melanoma of vagina--a case report with review of literature.

Primary vaginal malignant melanoma is a very rare tumor with less than 300 cases reported to date. We describe a case of primary vaginal melanoma and review the literature. A 60 years postmenopausal female patient presented with painless mass coming out of the vagina with occasional bleeding for last 2-3 weeks. On vaginal examination there was a firm polypoidal growth of size 7 cm attached to the right lateral wall of vagina and coming out of the introitus. Histopathology of the mass showed features of malignant melanoma. Wide local excision was done and adjuvant therapy was given. However patient came back after three months with widespread metastasis and expired 6 months after the initial diagnosis. Vaginal melanoma is a very aggressive tumor and the overall prognosis is very poor despite the treatment modality.

Electrocardiographic changes in lepra reaction.

The electrocardiographic (E.C.G.) changes were evaluated in 54 patients of lepra reaction. Abnormalities of the E.C.G. observed were in the form of prolongation of QTc in 24 (44.44%), ST-T changes in a (16.66%), bundle branch block and ventricular extrasystoles in 2 each (3.70%). The mean QTc interval in 64 normal adults was 0.41 second (S.D. +/- 0.03, range 0.36 to 0.44 second). It was 0.44 second (S.D. +/- 0.05, range 0.38 to 0.52 second) in patients of lepra reaction. The difference in the QTc values in the two groups was statistically significant (P less than 0.01). The E.C.G. abnormalities in patients of lepra reaction appears to be due to myocardial involvement.