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Background: As per statistics on infant mortality, the State of Maharashtra has done well in bringing down IMR from 33 to 16 per 1000 live births. However, in recent years many incidents come to light, especially in the case of institutional deliveries where newborns die either due to infrastructure failure or dysfunctional equipment. On a programmatic level, this has serious implications. Schemes such as Janani Suraksha Yojana promote institutional deliveries, but the institutes are unable to tend to the patient load efficiently. Analysing newspaper articles covering such incidents will throw light on actionable points for policy change. Experts from various fields tend to author such articles. Therefore it’s imperative to search every source available to bottleneck the areas for improvement. Objective: 1. To understand the perspectives of authors about newborn deaths in Maharashtra 2. To derive major areas of concern raised by such articles possibly causing newborn deaths in Maharashtra Methodology: All newspaper articles published in the last 2 years about newborn deaths in Maharashtra were identified. They were segregated according to the Name of the newspaper, author, incident, period etc. A thematic analysis was performed on 12 such articles to uncover different themes and sub themes. Results: Major themes that emerged were related to infrastructure issues and equipment failure. Another important theme was the higher patient load on secondary care due to excessive referrals from primary health facilities. The schemes promoting institutional deliveries did not anticipate the additional workload on district and subdistrict hospitals. Strengthening primary care remains the major area of concern. Conclusion: Lack of quality assurance is the major bottleneck at the infrastructure level. Strengthening primary care will reduce the excessive workload on district and subdistrict hospitals. All these are part of the same chain of events.

Abstract Some rare earth elements (REEs) are classified under critical materials, i.e., essential in use and subject to supply risk, due to their increasing demand, monopolistic supply, and environmentally unsustainable and expensive mining practices. To tackle the REE supply challenge, new initiatives have been started focusing on their extraction from alternative secondary resources. This study puts the emphasis on technospheric mining of REEs from bauxite residue (red mud) produced by the aluminum industry. Characterization results showed the bauxite residue sample contains about 0.03 wt% REEs. Systematic leaching experiments showed that concentrated HNO3 is the most effective lixiviant. However, because of the process complexities, H2SO4 was selected as the lixiviant. To further enhance the leaching efficiency, a novel process based on microwave pretreatment was employed. Results indicated that microwave pretreatment creates cracks and pores in the particles, enabling the lixiviant to diffuse further into the particles, bringing more REEs into solution, yielding of 64.2% and 78.7% for Sc and Nd, respectively, which are higher than the maximum obtained when HNO3 was used. This novel process of “H2SO4 leaching-coupled with-microwave pretreatment” proves to be a promising technique that can help realize the technological potential of REE recovery from secondary resources, particularly bauxite residue.

Ayurvedic powders are widely used as therapeutic agents but most of them have unpleasant taste and large doses. One of the possible approach to overcome these drawbacks is to represent them in unit dosage form i.e. tablet dosage form. The purpose of this study is to elucidate and quantify the compressibility and compactibility of herbal granules prepared by using hydrogel isolated from whole seeds of Ocimum basilicum as a novel binder. The compressibility is the ability of the powder to deform under pressure and the compactibility is the ability of a powder to form coherent compacts. To test the functionality of novel excipients, Sonnergaard proved a simple linear model to confirm compactability, which is an uncomplicated tool for quantification. The tablets were compressed at increasing compression pressures and were evaluated for various mechanical properties. The linear relationship between specific crushing strength and compression pressure revealed the compactibility of the herbal granules and the linear relationship between porosity and logarithm of compression pressure revealed the compressible nature of the herbal granules according to the model developed by Sonnergaard. Thus the hydrogel isolated from whole seeds of Ocimum basillicum had potential as a granulating and binding agent. [ABSTRACT FROM AUTHOR]

Reports on the treatment of three patients with AIDS who had disseminated infections with Mycobacterium (M.) kansasii. Number of patients with infection by M. kansasii who were identified in Illinois in 1982; Drug sensitivities of the patients.

Tracheal resection and reconstruction procedures are necessary when stenosis, tracheomalacia, tumors, vascular lesions, or tracheal injury cause a tracheal blockage. Replacement with a tracheal substitute is often recommended when the trauma exceeds 50% of the total length of the trachea in adults and 30% in children. Recently, tissue engineering and other advanced techniques have shown promise in fabricating biocompatible tracheal substitutes with physical, morphological, biomechanical, and biological characteristics similar to native trachea. Different polymers and biometals are explored. Even with limited success with tissue-engineered grafts in clinical settings, complete healing of tracheal defects remains a substantial challenge due to low mechanical strength and durability of the graft materials, inadequate re-epithelialization and vascularization, and restenosis. This review has covered a range of reconstructive and regenerative techniques, design criteria, the use of bioprostheses and synthetic grafts for the recovery of tracheal defects, as well as the traditional and cutting-edge methods of their fabrication, surface modification for increased immuno- or biocompatibility, and associated challenges., (© 2024 Wiley‐VCH GmbH.)

The healing of osteochondral defects (OCDs) that result from injury, osteochondritis, or osteoarthritis and bear lesions in the cartilage and bone, pain, and loss of joint function in middle- and old-age individuals presents challenges to clinical practitioners because of non-regenerative cartilage and the limitations of current therapies. Bioactive peptide-based osteochondral (OC) tissue regeneration is becoming more popular because it does not have the immunogenicity, misfolding, or denaturation problems associated with original proteins. Periodically, reviews are published on the regeneration of bone and cartilage separately; however, none of them addressed the simultaneous healing of these tissues in the complicated heterogeneous environment of the osteochondral (OC) interface. As regulators of cell adhesion, proliferation, differentiation, angiogenesis, immunomodulation, and antibacterial activity, potential therapeutic strategies for OCDs utilizing bone and cartilage-specific peptides should be examined and investigated. The main goal of this review was to study how they contribute to the healing of OCDs, either alone or in conjunction with other peptides and biomaterials.

Combinatorial molecular therapy in pancreatic ductal adenocarcinoma (PDAC) has yielded largely disappointing results in clinical testing to-date as a multitude of adaptive resistance mechanisms is making selection of patients via molecular markers that capture essential, intersecting signaling routes challenging. Here, we report the scaffolding protein connector enhancer of kinase suppressor of Ras 1 (CNKSR1) as mediator of resistance to MAPK (MEK) inhibition. MEK inhibition in CNKSR1high cancer cells induces translocation of CNKSR1 to the plasma membrane where the scaffolding protein interacts with and stabilizes the phosphorylated form of AKT. CNKSR1-mediated AKT activation following MEK inhibition was associated with increased cellular p-PRAS40 levels and reduced nuclear translocation and cellular levels of FoxO1, a negative regulator of AKT signaling. In clinical PDAC specimens, high cytoplasmatic CNKSR1 levels correlated with increased cellular phospho-AKT and mTOR levels. Pharmacological co-blockade of AKT and MEK ranked top in induced synergies with MEK inhibition in CNKSR1high pancreas cancer cells among other inhibitor combinations targeting known CNKSR1 signaling. In vivo, CNKSR1high pancreatic tumors treated with AKT and MEK inhibitors showed improved outcome in the combination arm compared with single-agent treatment, an effect not observed in CNKSR1low models.Our results identify CNKSR1 as regulator of adaptive resistance to MEK inhibition by promoting crosstalk to AKT signaling via a scaffolding function for the phosphorylated form of AKT. CNSKR1 expression might be a possible molecular marker to enrich patients for future AKT-MEK inhibitor precision medicine studies., Implications: The CNKSR1 scaffold, identified within an RNAi screen as a novel mediator of resistance to MEK inhibition in pancreas cancer, connects the MAPK pathway and AKT signaling and may be adopted as a biomarker to select patients for combined MEK AKT blockade., (©2023 The Authors; Published by the American Association for Cancer Research.)

Peptides were designed to inhibit the protein-protein interaction of CD2 and CD58 to modulate the immune response. This work involved the design and synthesis of eight different peptides by replacing each amino acid residue in peptide 6 with alanine as well as grafting the peptide to the sunflower trypsin-inhibitor framework. From the alanine scanning studies, mutation at position 2 of the peptide was shown to result in increased potency to inhibit cell adhesion interactions. The most potent peptide from the alanine scanning was further studied for its detailed three-dimensional structure and binding to CD58 protein using surface plasmon resonance and flow cytometry. This peptide was used to graft to the sunflower trypsin inhibitor to improve the stability of the peptide. The grafted peptide, SFTI-a1, was further studied for its potency as well as its thermal, chemical, and enzymatic stability. The grafted peptide exhibited improved activity compared to our previously grafted peptide and was stable against thermal and enzymatic degradation., (© 2020 John Wiley & Sons A/S.)

Purpose: To describe the seizure pattern, treatment strategies and outcome in a series of children with Rolandic seizures or childhood epilepsy with centrotemporal spikes., Materials and Methods: Patients were defined as Rolandic epilepsy if on electroencephalographic studies high voltage spike and waves were seen in centrotemporal areas, could be followed by slow waves, often activated on sleep and could shift from one side to other or be secondarily generalized. Typical (TRS) or benign were those with normal intellect. Atypical rolandic seizures (ARS) were those associated with neuroregression of language and cognitive milestones. Patients were treated with antiepileptic drugs if more than one episode occurred or the first episode was generalized status epilepticus., Results: Thirty-three patients were included over the period of eight years (2012-2020). There was male preponderance (21 males versus 12 females). Four patients (12.12%) later evolved into Landau Kleffner syndrome (ARS group). The mean age of onset of epilepsy in the TRS group (29 patients) was 7.2 (+/-2.2) with the youngest patient being 4 years and the eldest being 12 years. In the ARS group the mean age of onset was 5 yrs. (+/-1.41). In the TRS group, 23 (79.31%) patients were managed on monotherapy AED. Seventeen patients (58.62%) responded (remission) to carbamazepine monotherapy alone. Six patients (20.68%) could afford oxcarbazepine monotherapy and went in remission with this therapy. In the ARS group all patients required three drugs (valproate, clobazam and levetiracetam). By the end of the study period, 23/33 (75.75%) patients remained seizure free., Conclusions: Most patients with rolandic seizures have excellent prognosis being seizure free around puberty. The neurological outcome in most patients was normal., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the mannose receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182-mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206 high patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased cancer cell phagocytosis by reprogrammed TAMs., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Protein-protein interactions (PPI) by homo-, hetero- or oligo-merization in the cellular environment regulate cellular processes. PPI can be inhibited by antibodies, small molecules or peptides, and this inhibition has therapeutic value. A recently developed method, the proximity ligation assay (PLA), provides detection of PPI in the cellular environment. However, most applications using this assay are for proteins expressed in the same cell. We employ PLA for the first time to study PPI of cell surface proteins on two different cells. Inhibition of PPI using a peptide inhibitor is also quantified using this assay; PLA is used to detect PPI of CD2 and CD58 between Jurkat cells (T cells) and human fibroblast-like synoviocyte-rheumatoid arthritis cells that are important in the immune response in the autoimmune disease rheumatoid arthritis. This assay provides direct evidence of inhibition of PPI of two proteins on different cell surfaces.

HER2 receptors are surface proteins belonging to the epidermal growth factor family of receptors. Their numbers are elevated in breast, lung, and ovarian cancers. HER2-positive cancers are aggressive, have higher mortality rate, and have a poor prognosis. We have designed peptidomimetics that bind to HER2 and block the HER2-mediated dimerization of epidermal growth factor family of receptors. Among these, a symmetrical cyclic peptidomimetic (compound 18) exhibited antiproliferative activity in HER2-overexpressing lung cancer cell lines with IC 50 values in the nanomolar concentration range. To improve the stability of the peptidomimetic, d-amino acids were introduced into the peptidomimetic, and several analogs of compound 18 were designed. Among the analogs of compound 18, compound 32, a cyclic, d-amino acid-containing peptidomimetic, was found to have an IC 50 value in the nanomolar range in HER2-overexpressing cancer cell lines. The antiproliferative activity of compound 32 was also measured by using a 3D cell culture model that mimics the in vivo conditions. The binding of compound 32 to the HER2 protein was studied by surface plasmon resonance. In vitro stability studies indicated that compound 32 was stable in serum for 48 hours and intact peptide was detectable in vivo for 12 hours. Results from our studies indicated that 1 of the d-amino acid analogs of 18, compound 32, binds to the HER2 extracellular domain, inhibiting the phosphorylation of kinase of HER2., (Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.)

Colorectal cancer (CRC) is the third most common solid internal malignancy among cancers. Early detection of cancer is key to increasing the survival rate of colorectal cancer patients. Overexpression of the EGFR protein is associated with CRC. We have designed a series of peptides that are highly specific for the extracellular domain of EGFR, based on our earlier studies on linear peptides. The previously reported linear peptide LARLLT, known to bind to EGFR, was modified with the goals of increasing its stability and its specificity toward EGFR. Peptide modifications, including D-amino acid substitution, cyclization, and chain reversal, were investigated. In addition, to facilitate labeling of the peptide with a fluorescent dye, an additional lysine residue was introduced onto the linear (KLARLLT) and cyclic peptides cyclo(KLARLLT) (Cyclo.L1). The lysine residue was also converted into an azide group in both a linear and reversed cyclic peptide sequences cyclo(K(N3)larllt) (Cyclo.L1.1) to allow for subsequent "click" conjugation. The cyclic peptides showed enhanced binding to EGFR by SPR. NMR and molecular modeling studies suggest that the peptides acquire a β-turn structure in solution. In vitro stability studies in human serum show that the cyclic peptide is more stable than the linear peptide., (© 2017 John Wiley & Sons A/S.)

Among different types of EGFR dimers, EGFR-HER2 and HER2-HER3 are well known in different types of cancers. Targeting dimerization of EGFR will have a significant impact on cancer therapies. A symmetric peptidomimetic was designed to inhibit the protein-protein interaction of EGFR. The peptidomimetic (Cyclo(1,10)PpR ( R ) Anapa-FDDF-( R )-Anapa)R, compound 18) was shown to exhibit antiproliferative activity with an IC 50 of 194 nM in HER2-expressing breast cancer cell lines and 18 nM in lung cancer cell lines. The peptidomimetic has a Pro-Pro sequence in the structure to stabilize the β-turn and a β-amino acid, amino napthyl propionic acid. To investigate the effect of the chirality of β-amino acid on the structure of the peptide and its antiproliferative activity, diastereoisomers of compound 18 were designed and synthesized. Structure-activity relationships of these compounds indicated that there is a chiral switch at β-amino acid in the designed compound. The peptidomimetic with R configuration at β-amino acid and with a L-Pro-D-Pro sequence was the most active compound (18). Using enzyme complement fragmentation assay and proximity ligation assay, we show that compound 18 inhibits HER2:HER3 and EGFR:HER2 dimerization. Surface plasmon resonance studies suggested that compound 18 binds to the HER2 extracellular domain and in particular to domain IV. The anticancer activity of compound 18 was evaluated using a xenograft model of breast cancer in mice; compound 18 suppressed the tumor growth in mice compared to control. Compound 18 was also shown to have a synergistic effect with erlotinib on EGFR mutated lung cancer cell lines., Competing Interests: CONFLICTS OF INTEREST None.

Nature provides a variety of peptides that are expressed in most living species. Evolutionary pressure and natural selection have created and optimized these peptides to bind to receptors with high affinity. Hence, natural resources provide an abundant chemical space to be explored in peptide-based drug discovery. Marine peptides can be extracted by simple solvent extraction techniques. The advancement of analytical techniques has made it possible to obtain pure peptides from natural resources. Extracted peptides have been evaluated as possible therapeutic agents for a wide range of diseases, including antibacterial, antifungal, antidiabetic and anticancer activity as well as cardiovascular and neurotoxin activity. Although marine resources provide thousands of possible peptides, only a few peptides derived from marine sources have reached the pharmaceutical market. This review focuses on some of the peptides derived from marine sources in the past ten years and gives a brief review of those that are currently in clinical trials or on the market.

Doxorubicin (DOX) belongs to the anthracycline class of drugs that are used in the treatment of various cancers. It has limited cystostatic effects in therapeutic doses, but higher doses can cause cardiotoxicity. In the current approach, we conjugated a peptidomimetic (Arg-aminonaphthylpropionic acid-Phe, compound 5) known to bind to HER2 protein to DOX via a glutaric anhydride linker. Antiproliferative assays suggest that the DOX-peptidomimetic conjugate has activity in the lower micromolar range. The conjugate exhibited higher toxicity in HER2-overexpressed cells than in MCF-7 and MCF-10A cells that do not overexpress HER2 protein. Cellular uptake studies using confocal microscope experiments showed that the conjugate binds to HER2-overexpressed cells and DOX is taken up into the cells in 4 h compared to conjugate in MCF-7 cells. Binding studies using surface plasmon resonance indicated that the conjugate binds to the HER2 extracellular domain with high affinity compared to compound 5 or DOX alone. The conjugate was stable in the presence of cells with a half-life of nearly 4 h and 1 h in human serum. DOX is released from the conjugate and internalized into the cells in 4 h, causing cellular toxicity. These results suggest that this conjugate can be used to target DOX to HER2-overexpressing cells and can improve the therapeutic index of DOX for HER2-positive cancer., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The interaction between the cell-cell adhesion proteins CD2 and CD58 plays a crucial role in lymphocyte recruitment to inflammatory sites, and inhibitors of this interaction have potential as immunomodulatory drugs in autoimmune diseases. Peptides from the CD2 adhesion domain were designed to inhibit CD2:CD58 interactions. To improve the stability of the peptides, β-sheet epitopes from the CD2 region implicated in CD58 recognition were grafted into the cyclic peptide frameworks of sunflower trypsin inhibitor and rhesus theta defensin. The designed multicyclic peptides were evaluated for their ability to modulate cell-cell interactions in three different cell adhesion assays, with one candidate, SFTI-a, showing potent activity in the nanomolar range (IC50: 51 nM). This peptide also suppresses the immune responses in T cells obtained from mice that exhibit the autoimmune disease rheumatoid arthritis. SFTI-a was resistant to thermal denaturation, as judged by circular dichroism spectroscopy and mass spectrometry, and had a half-life of ∼24 h in human serum. Binding of this peptide to CD58 was predicted by molecular docking studies and experimentally confirmed by surface plasmon resonance experiments. Our results suggest that cyclic peptides from natural sources are promising scaffolds for modulating protein-protein interactions that are typically difficult to target with small-molecule compounds.

CD2 and CD58 are two important costimulatory molecules involved in generating the signal II required for normal immune signaling. However, this interaction can be targeted to be of benefit in cases of abnormal immune signaling seen in autoimmune diseases. Our objective in this study was to design a peptidomimetic (compound 7) based on a β-strand structure of the adhesion domain of CD2 protein to inhibit CD2-CD58 protein-protein interaction and its effect on immunomodulation in the collagen-induced arthritis (CIA) model. The ability of compound 7 to bind to CD58 protein was assessed using flow cytometry. The effect of compound 7 on modulating the immune response was evaluated in an autoimmune disease using CIA in mice. The stability of compound 7 was evaluated in mouse serum using mass spectrometry. Antibody (Ab) binding inhibition studies suggested that compound 7 binds to CD58 protein. Compound 7 was successful in modulating immune responses when administered in the CIA mouse model along with reducing anti-collagen Ab levels and decreasing the level of interferon gamma (IFN-γ) relative to control treatments. Compound 7 was found to be nonimmunogenic and stable in mouse serum up to 48 h. Results suggest that compound 7 can serve as a lead compound for immunomodulation, and could be a therapeutic agent for the autoimmune disease rheumatoid arthritis (RA)., (© 2015 Wiley Periodicals, Inc.)

Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

Objectives: The objective of this study is to evaluate and to compare the tensile weld strengths and microstructural changes in four archwires namely beta titanium, stainless steel (SS), blue elgiloy and timolium before and after immersion in 1.23% acidulated phosphate fluoride (APF) solution., Materials and Methods: The mean tensile weld strength of a weld joint of four arch wires were compared pre-fluoride (Group 1) with post fluoride (Group 2) and the microstructural characteristics of weld joints were evaluated under an optical microscope., Results: The mean tensile weld strength for beta titanium was 445.64 N/mm 2, blue elgiloy was 363.26 N/mm 2, SS was 358.30 N/mm 2 and timolium was 308.62 N/mm 2. After immersion in fluoride the mean tensile strength for beta titanium was 427.16 N/mm 2, blue elgiloy was 359.86 N/mm 2, SS is 349.44 N/mm 2 and timolium is 294.86 N/mm 2. After immersion in fluoride, the beta titanium and SS had a smooth fusion at the center of weld assembly with characteristic nugget formation. The beta titanium weld assembly had greater tensile weld strength than other welded assemblies. Blue elgiloy ranked second, whereas SS and timolium were third and fourth respectively., Conclusion: The wires in descending order of their mean tensile weld strength, on evaluation of their weld joints were found to be: Beta titanium > blue elgiloy > SS > timolium. The reduction in tensile weld strength was statistically insignificant for all the archwires after exposure to 1.23% APF at 37°C for 90 min.

Objective: To determine if the mandibular condylar cartilage (MCC) will grow with and without mandibular anterior repositioning appliances with the administration of insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β)., Materials and Methods: Twenty-four growing New Zealand rabbits were divided into three groups: a group with saline injection in the temporomandibular joint, a group that received anterior positioning appliance, and a group that received injection of growth factors as well as mandibular repositioning appliance. Real-time reverse transcription polymerase chain reaction technique was used to study gene expression supported by histomorphometry., Results: Administration of growth factors along with mandibular repositioning appliances has induced 5.70-fold expression of matrix metalloproteinase-1 (MMP-1) (P < .0005) and 1.29-fold expression of MMP-13 (P < .0005). In contrast, administration of mandibular repositioning appliances only has induced 2.33-fold expression of MMP-1 (P < .0005) and 0.83-fold expression of MMP-13 (P < .0005). Histomorphometric analysis revealed increased proliferation of the condylar cartilage in the appliance and injection group as compared to the control group., Conclusion: The administration of growth factors along with the use of mandibular advancement appliance has increased genetic expression of MMP-1 and MMP-13 supported by histomorphometric evidence indicating growth of condylar cartilage.

In this study, we aimed to correlate the analytical performance of SD BIOLINE TB Ag MPT64 Rapid Test kit (MPT64 assay) with the mycobacterial growth unit (GU) reported by the BACTEC MGIT 960 (MGIT 960) instrument. A total of 394 culture isolates reported positive by MGIT 960 were processed daily (until 'day 4') with the MPT64 assay until a positive MPT64 result was obtained and their GU values were noted daily before MPT64 testing. Based on this correlation of MPT64 positivity and corresponding GU values, a GU cut-off was determined. In the validation phase, with the experimentally determined GU cut-off value, 99.1% (576/581) of culture isolates were correctly identified as MTB within 2 days from instrument positivity. All results were available using a single-MPT64 assay strip, making the assay cost-effective. Thus, systematic implementation of the MPT64 assay proved to be cost-effective in a high-throughput laboratory without any delay in patient reporting., (Copyright © 2012 Elsevier Inc. All rights reserved.)

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.

Vascular endothelial growth factor (VEGF), initially detected in bovine pituitary follicular cells, is widely localized in hypertrophic zones of chondrocytes in various tissues where focus is on bone growth. Similarly, VEGF found in chondrocytes of articular cartilage of osteo-arthritic/rheumato-arthritic joints reflected need for bone repair. Members of VEGF family of human origin are seven homo-dimeric, heparin-binding glyco-proteins, encoded by different genes located on different chromosomes. They encode seven isoforms: VEGF-A, -B, -C, -D, -E, -F, and PLGF, each catalyzing distinct functions. They are compared with VEGFs derived from bovine origin in biochemical composition and functions. Each isoform and subtype has specific receptors for binding, necessary for expression of specific functions in bone growth or repair. VEGF control is by diffusion of isoforms, hypoxic conditions, and bone (mandibular) positioning. Thus, transformation of cartilage into bone involves proliferation of mesenchymal cells, hypertrophy in chondrocytes, capillary invasion, and calcification by extra cellular matrix (ECM). Inherent limitations of in vitro/in vivo models and chronology of appearance of different isoforms have eluded precise mechanism of VEGF action and regulation. Nonetheless, central role of VEGF in bone growth is quite obvious., (Copyright © 2011 Wiley Periodicals, Inc.)

Tuberculosis of the distal colon occurring in the absence of ileocecal or pulmonary involvement is often mistaken for neoplasm or Crohn's disease. In spite of various studies, including colonoscopy and brushings with biopsy, the diagnosis might still be in doubt at the time of operation. The combined approach of surgery and chemotherapy appears to be the treatment of choice, especially in those patients who have bleeding and/or obstruction in whom the diagnosis cannot be made by other modalities.

A patient had obstruction of the right and left hepatic ducts secondary to perforate diaphragms at the junction with the common hepatic duct. Transhepatic cholangiograms of both the right and left lobes were required to define the presence of diaphragms at the junctions of right, left, and common hepatic ducts. Excision of the diaphragms relieved the obstruction. A distinction should be made between congenital nonobstructive and congenital obstructive cystic dilation of intrahepatic biliary radicals.

The association of abnormalities of the common bile duct with chronic inflammatory disease of the pancreas is described in this report in which the important diagnostic role of endoscopic retrograde cholangiopancreatography (ERCP) is emphasized in this disease entity. ERCP was utilized as a single diagnostic modality in 27 patients (15 females) in whom both the biliary tree and pancreatic ducts were demonstrated. Abnormalities of the pancreatic duct were noted in all patients while the associated changes of the common bile duct were noted in 12 (44%--7 females). The role of ERCP in confirming the diagnosis and its importance in planning specific therapy is emphasized.

Fifty patients (29 females) undergoing ERCP were studied prospectively for the occurrence of bacteremia associated with this endoscopic procedure. Each patient had blood samples drawn for aerobic and anaerobic cultures before endoscopy, after entering the duodenum, 5 and 15 minutes after cannulation of the papilla of Vater. Subcultures were made at 24 and 48 hours for a total of 1,200 cultures. No positive cultures were obtained in 48 patients. One patient developed a Staphylococcus epidermidis bacteremia during the procedure. The cleansing technic for the instruments consisted of alcohol and water only. Prophylactic antiobiotics were not administered. In contrast to other gastrointestinal procedures, our results suggest that bacteremia is an uncommon occurrence in ERCP despite the longer duration of the procedure and instrumentation of a sterile duct system.