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1.  Thrombosed prosthetic mitral valve 
BMJ Case Reports  2012;2012:bcr1020115002.
PMCID: PMC3316824  PMID: 22605815
2.  Reconstruction of the chin using an expanded deltopectoral flap following multiple recurrences of oral cancer 
An important alternative to free tissue transfer in patients requiring correction of soft tissue chin defects are local and regional flaps, such as the pectoralis major myocutaneous flap and deltopectoral flap. With predictable vascular supply, potential for large size, and good aesthetic match for facial and cervical skin, the deltopectoral flap can offer the reconstructive surgeon additional options in patients who lack vessels suitable for free tissue transfer. The use of an expanded deltopectoral flap for a staged reconstruction of the chin in a patient with cancer recurrences, concomitant resections, radiation and multiple reconstructions is reported.
PMCID: PMC3433825  PMID: 23997595
Chin reconstruction; Deltopectoral
3.  Giant lipomas of the upper extremity: Case reports and a literature review 
Giant fibrolipomas involving the upper extremities are rare tumours. These large masses grow slowly and produce symptoms due to their size, location and compression of adjacent structures. Surgical excision usually leads to complete recovery from symptoms.
PMCID: PMC3433826  PMID: 23997596
Giant lipoma
4.  Intraneural lipoma of the ulnar nerve at the elbow: A case report and literature review 
Intraneural lipomas of the ulnar nerve or its branches are rare benign tumours. Although most intraneural lipomas present as asymptomatic tumours, some may present as compression neuropathies due to their location. In the majority of cases these tumours can be enucleated without damage to the nerve fibres.
PMCID: PMC3433827  PMID: 23997597
Intraneural lipoma; Ulnar nerve
5.  Acute carpal tunnel syndrome from burns of the hand and wrist 
Acute median nerve compression usually occurs from increased pressure within the carpal tunnel and forearm compartments. Although the hyperesthesia from burns may mimic symptoms of acute compression neuropathy, clinical diagnosis should be made from history, clinical signs and symptoms. Early recognition and decompression of the carpal tunnel either as part of the burn excision or along with escharotomy usually leads to full recovery.
PMCID: PMC2827286  PMID: 21119830
Burns of hands and wrist; Median nerve compression neuropathy
6.  Intraneural lipoma of the radial nerve presenting as Wartenberg syndrome: A case report and review of literature 
The superficial branch of the radial nerve is highly vulnerable to trauma, irritation and compression due to its anatomical location. Intraneural lipomas and fibrolipomas arising from the supporting tissues of this peripheral nerve can cause compression of the adjacent nerve leading to symptoms of neuritis of the radial nerve or Wartenberg syndrome.
PMCID: PMC2827289  PMID: 21119833
Intraneural lipoma; Wartenberg syndrome
7.  Faecal bifidobacteria in Indian neonates & the effect of asymptomatic rotavirus infection during the first month of life 
Background & Objectives:
Bifidobacteria colonize the gut after the first week of life and remain an important component of the gut microbiota in infancy. This study was carried out to characterize the diversity and number of bifidobacteria colonizing the gut in Indian neonates and to investigate whether asymptomatic infection with rotavirus in the first month of life affected gut colonization by bidifobacteria.
DNA was isolated from faeces of 14 term-born neonates who were under surveillance for rotavirus infection. Bacterial and bifidobacterial diversity was evaluated by temporal temperature gradient electrophoresis (TTGE) of 16S rDNA amplified using total bacteria and bifidobacteria-specific primers. Real time PCR, targeting 16S rDNA, was used to quantitate faecal bifidobacteria and enterobacteria.
TTGE of conserved bacterial 16S rDNA showed 3 dominant bands of which Escherichia coli (family Enterobacteriaceae) and Bifidobacterium (family Bifidobacteriaceae) were constant. TTGE of Bifidobacterium genus-specific DNA showed a single band in all neonates identified by sequencing as Bifidobacterium longum subsp. infantis. Faecal bifidobacterial counts (log10 cfu/g faeces) ranged from 6.1 to 9.3 and enterobacterial counts from 6.3 to 9.5. Neonates without and with rotavirus infection in the first week of life did not show significant differences in the median count of bifidobacteria (log10 count 7.48 vs. 7.41) or enterobacteria (log10 count 8.79 vs. 7.92).
Interpretation & Conclusions:
B. longum subsp. infantis was the sole bifidobacterial species colonizing the gut of Indian neonates. Asymptomatic rotavirus infection in the first month of life was not associated with alteration in faecal bifidobacteria or enterobacteria.
PMCID: PMC3102461  PMID: 21245621
Bifidobacterium; colonization; gut; neonates; rotavirus
8.  Reconstruction of sacral defects following necrosis of buttocks due to embolization of internal iliac artery using a transverse lumbar flap 
Fractures of the pelvis associated with uncontrollable hypotension are managed by stabilization of fractures and arteriographic embolization of the bleeding vessels. Embolization of these arteries may result in necrosis of the buttocks. The use of a transverse lumbar artery-based flap can be used for repair of these defects.
PMCID: PMC2740608  PMID: 20808748
Transverse lumbar flap
9.  Reversed dorsal metatarsal artery flap for reconstruction of a soft tissue defect of the big toe 
Soft tissue defects of the great toe that include exposed tendon and bone present a reconstructive challenge for plastic surgeons. A distally based dorsalis pedis island flap based on the first dorsal metatarsal artery, which has been successfully used to cover the soft tissue defect following wide excision of melanoma of the big toe, is reported
PMCID: PMC2740609  PMID: 20808742
Dorsal metatarsal artery flap
10.  Acute carpal tunnel syndrome as a result of spontaneous bleeding 
Acute carpal tunnel syndrome is the most common compression neuropathy of the upper extremity following trauma. A rare occurence of spontaneous bleeding into the carpal tunnel, presenting as acute carpal tunnel syndrome, is presented.
PMCID: PMC2691013  PMID: 19721797
Carpal tunnel syndrome; Spontaneous bleeding
11.  MiR-494 Within an Oncogenic MicroRNA Megacluster Regulates G1/S Transition in Liver Tumorigenesis Through Suppression of MCC 
Hepatology (Baltimore, Md.)  2013;59(1):10.1002/hep.26662.
Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver’s unique affinity for small nucleic acids, miRNA based therapy has been proposed in the treatment of liver disease. There is thus an urgent need to identify and characterize aberrantly expressed miRNAs in HCC. In our study, we profiled miRNA expression changes in de novo liver tumors driven by MYC and/or RAS, two canonical oncogenes activated in a majority of human HCC. We identified an upregulated miRNA megacluster comprised of 53 miRNAs on mouse chromosome 12qF1 (human homolog 14q32). This miRNA megacluster is upregulated in all three transgenic liver models and in a subset of human HCCs. An unbiased functional analysis of all miRNAs within this cluster was performed.
We found that miR-494 is overexpressed in human HCC, and aids in transformation by regulating the G1/S cell cycle transition through targeting of the Mutated in Colorectal Cancer (MCC) tumor suppressor. miR-494 inhibition in human HCC cell lines decreases cellular transformation and anti-miR-494 treatment of primary MYC-driven liver tumor formation significantly diminishes tumor size. Our findings identify a new therapeutic target, miR-494, for the treatment of HCC.
PMCID: PMC3877416  PMID: 23913442
HCC; cancer; cell cycle; Dlk1-Dio3; miRNA therapy
12.  High Prevalence of Hepatitis Delta Virus among Patients with Chronic Hepatitis B Virus Infection and HIV-1 in an Intermediate Hepatitis B Virus Endemic Region 
We conducted a study to investigate HIV and hepatitis delta virus (HDV) coinfection among patients with chronic hepatitis B virus (HBV) infection and the triple infection’s (HIV/HBV/HDV) clinical implications in India, an intermediate HBV endemic region, with an estimated HIV-positive population of 2.5 million. A total of 450 patients (men: 270; women: 180) with chronic HBV infections and 135 healthy volunteers were screened for HIV and HDV. The incidence of the triple infection was low (4 [0.8%]) compared with dual infections of HIV-1/HBV (7 [1.5%]) and HBV/HDV (22[4.8%]). Among 21- to 40-year-olds, HBV/HDV coinfection (45.8%) and HBV/HDV/HIV-1 triple infection was predominant (75%). Among 11 patients coinfected with HIV-1/HBV, 4 (36%) were tri-infected and were also associated with chronic hepatitis and cirrhosis. The HDV coinfection was higher among patients coinfected with HBV/HIV-1, despite the declining trend in HDV infection among HIV-negative patients, as previously reported. Thus, it is important to assess the impact of HIV, chronic HBV, and HDV tri-infection in India.
PMCID: PMC4114572  PMID: 23722085
coinfection in India; hepatitis delta virus (HDV); hepatitis B virus (HBV); human immunodeficiency virus (HIV)
13.  Sonographic evaluation of intravascular volume status: Can internal jugular or femoral vein collapsibility be used in the absence of IVC visualization? 
Annals of Thoracic Medicine  2015;10(1):44-49.
Inferior vena cava collapsibility index (IVC-CI) has been shown to correlate with both clinical and invasive assessment of intravascular volume status, but has important limitations such as the requirement for advanced sonographic skills, the degree of difficulty in obtaining those skills, and often challenging visualization of the IVC in the postoperative patient. The current study aims to explore the potential for using femoral (FV) or internal jugular (IJV) vein collapsibility as alternative sonographic options in the absence of adequate IVC visualization.
A prospective, observational study comparing IVC-CI and Fem- and/or IJV-CI was performed in two intensive care units (ICU) between January 2012 and April 2014. Concurrent M-mode measurements of IVC-CI and FV- and/or IJV-CI were collected during each sonographic session. Measurements of IVC were obtained using standard technique. IJV-CI and FV-CI were measured using high-frequency, linear array ultrasound probe placed in the corresponding anatomic areas. Paired data were analyzed using coefficient of correlation/determination and Bland-Altman determination of measurement bias.
We performed paired ultrasound examination of IVC-IJV (n = 39) and IVC-FV (n = 22), in 40 patients (mean age 54.1; 40% women). Both FV-CI and IJV-CI scans took less time to complete than IVC-CI scans (both, P < 0.02). Correlations between IVC-CI/FV-CI (R2 = 0.41) and IVC-CI/IJV-CI (R2 = 0.38) were weak. There was a mean -3.5% measurement bias between IVC-CI and IJV-CI, with trend toward overestimation for IJV-CI with increasing collapsibility. In contrast, FV-CI underestimated collapsibility by approximately 3.8% across the measured collapsibility range.
Despite small measurement biases, correlations between IVC-CI and FV-/IJV-CI are weak. These results indicate that IJ-CI and FV-CI should not be used as a primary intravascular volume assessment tool for clinical decision support in the ICU. The authors propose that IJV-CI and FV-CI be reserved for clinical scenarios where sonographic acquisition of both IVC-CI or subclavian collapsibility are not feasible, especially when trended over time. Sonographers should be aware that IJV-CI tends to overestimate collapsibility when compared to IVC-CI, and FV-CI tends to underestimates collapsibility relative to IVC-CI.
PMCID: PMC4286845  PMID: 25593607
Femoral vein; hemodynamic resuscitation; intensive care unit; internal jugular vein; inferior vena cava; intravascular volume status assessment; portable ultrasound; point-of-care testing; venous collapsibility index
14.  Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis 
Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF). However, its role in interstitial lung disease (ILD) due to other causes such as systemic sclerosis (SSc) is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.
PMCID: PMC4298919  PMID: 25624597
Interstitial lung disease; pirfenidone; systemic sclerosis
15.  Pleuropulmonary melioidosis with osteomyelitis rib 
Melioidosis is a multiorgan infectious disease caused by Burkholderia pseudomallei. Few cases have been reported from south India. This is a case report of pleuropulmonary melioidosis with rib osteomyelitis.
PMCID: PMC4298925  PMID: 25624602
Burkholderia pseudomallei; melioidosis; pleuropulmonary
16.  Enzyme-Assisted Extraction of Bioactive Material from Chondrus crispus and Codium fragile and Its Effect on Herpes simplex Virus (HSV-1) 
Marine Drugs  2015;13(1):558-580.
Codium fragile and Chondrus crispus are, respectively, green and red seaweeds which are abundant along the North Atlantic coasts. We investigated the chemical composition and antiviral activity of enzymatic extracts of C. fragile (CF) and C. crispus (CC). On a dry weight basis, CF consisted of 11% protein, 31% neutral sugars, 0.8% sulfate, 0.6% uronic acids, and 49% ash, while CC contained 27% protein, 28% neutral sugars, 17% sulfate, 1.8% uronic acids, and 25% ash. Enzyme-assisted hydrolysis improved the extraction efficiency of bioactive materials. Commercial proteases and carbohydrases significantly improved (p ≤ 0.001) biomass yield (40%–70% dry matter) as compared to aqueous extraction (20%–25% dry matter). Moreover, enzymatic hydrolysis enhanced the recovery of protein, neutral sugars, uronic acids, and sulfates. The enzymatic hydrolysates exhibited significant activity against Herpes simplex virus (HSV-1) with EC50 of 77.6–126.8 μg/mL for CC and 36.5–41.3 μg/mL for CF, at a multiplicity of infection (MOI) of 0.001 ID50/cells without cytotoxity (1–200 μg/mL). The extracts obtained from proteases (P1) and carbohydrases (C3) were also effective at higher virus MOI of 0.01 ID50/cells without cytotoxity. Taken together, these results indicate the potential application of enzymatic hydrolysates of C. fragile and C. crispus in functional food and antiviral drug discovery.
PMCID: PMC4306952  PMID: 25603348
Codium fragile; Chondrus crispus; red seaweeds; sulfates; Herpes simplex virus (HSV-1)
17.  Multifaceted Adult T-Cell Leukemia/Lymphoma in India: A Case Series 
Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell lymphotropic virus type-1 (HTLV-1). India is considered as a nonendemic region for HTLV-1. Recent upsurge of cases have been noted in southern parts of India.
Aims and objectives:
The objective was to describe skin manifestations in various types of ATL.
Materials and Methods:
Clinical examination, blood investigations, skin biopsies, lymph node biopsies, and immunohistochemistry were performed in five patients. Flow cytometry was performed in two cases.
Serological testing was positive for HTLV-1 in all patients. All patients presented with skin lesions. Rare presentations of molluscum contagiosum like papules, purpuric macules and plaques, hypopigmented macules and verrucous papules were seen. Dermatophytic infections occurred in two patients. Mucosal lesion was seen in one patient. Histological features include dermal lymphoid infiltrate with or without epidermotropism. Presence of epidermotropism did not correlate with the severity of disease. All patients except one succumbed to illness within few months to 1 year period.
ATL manifest in myriad presentations and skin lesions are often the earliest manifestation. Cutaneous manifestations of ATL vary from subtle hypopigmented macules to florid nodular lesions, and HTLV-1 screening need to be carried out in all doubtful cases.
PMCID: PMC4318027  PMID: 25657421
Adult T-cell leukemia/lymphoma; India; skin lesions
18.  Use of europium ions for SAD phasing of lysozyme at the Cu Kα wavelength 
Acta Crystallographica Section F  2012;69(Pt 1):20-24.
Europium(III) ions bound to the surface of hen egg-white lysozyme were found to exhibit good anomalous signal facilitating SAD phasing using laboratory-source data and automated model building. The europium ion-binding sites were observed up to the 15σ level.
Europium is shown to be a good anomalous scatterer in SAD phasing for solving the structure of biological macromolecules. The large value of the anomalous contribution of europium, f′′ = 11.17 e−, at the Cu Kα wavelength is an advantage in de novo phasing and automated model building. Tetragonal crystals of hen egg-white lysozyme (HEWL) incorporating europium(III) chloride (50 mM) were obtained which diffracted to a resolution of 2.3 Å at a wavelength of 1.54 Å (Cu Kα). The master data set (360° frames) was split and analyzed for anomalous signal-to-noise ratio, multiplicity, completeness, SAD phasing and automated building. The structure solution and model building of the split data sets were carried out using phenix.autosol and phenix.autobuild. The contributions of the Eu ions to SAD phasing using in-house data collection are discussed. This study revealed successful lysozyme phasing by SAD using laboratory-source data involving Eu ions, which are mainly coordinated by the side chains of Asn46, Asp52 and Asp101 together with some water molecules.
PMCID: PMC3539697  PMID: 23295480
europium; SAD; lysozyme
19.  Lipoamide channel-binding sulfonamides selectively inhibit mycobacterial lipoamide dehydrogenase†,# 
Biochemistry  2013;52(51):9375-9384.
Tuberculosis remains a global health emergency that calls for treatment regimens directed at new targets. Here we explored lipoamide dehydrogenase, a metabolic and detoxifying enzyme in Mycobacterium tuberculosis whose deletion drastically impairs Mtb's ability to establish infection in the mouse. Upon screening over 1,600,000 compounds, we identified N-methylpyridine 3-sulfonamides as potent and species-selective inhibitors of Mtb Lpd, affording over 1,000-fold selectivity versus the human homolog. The sulfonamides demonstrated low nanomolar affinity and bound at the lipoamide channel in an Lpd-inhibitor co-crystal. Their selectivity could be attributed, at least partially, to hydrogen bonding of the sulfonamide amide oxygen with the species-variant Arg93 in the lipoamide channel. Although potent and selective, the sulfonamides did not enter mycobacteria, as determined by their inability to accumulate in Mtb to effective levels and produce changes in intracellular metabolites. This work demonstrates that high potency and selectivity can be achieved at the lipoamide binding site of Mtb Lpd, a site different from the NAD+/NADH pocket targeted by previously reported species-selective triazaspirodimethoxybenzoyl inhibitors.
PMCID: PMC3894633  PMID: 24251446
20.  A Comparative Study on Visual Choice Reaction Time for Different Colors in Females 
Reaction time is one of the important methods to study a person's central information processing speed and coordinated peripheral movement response. Visual choice reaction time is a type of reaction time and is very important for drivers, pilots, security guards, and so forth. Previous studies were mainly on simple reaction time and there are very few studies on visual choice reaction time. The aim of our study was to compare the visual choice reaction time for red, green, and yellow colors of 60 healthy undergraduate female volunteers. After giving adequate practice, visual choice reaction time was recorded for red, green, and yellow colors using reaction time machine (RTM 608, Medicaid, Chandigarh). Repeated measures of ANOVA and Bonferroni multiple comparison were used for analysis and P < 0.05 was considered statistically significant. The results showed that both red and green had significantly less choice visual choice reaction (P values <0.0001 and 0.0002) when compared with yellow. This could be because individual color mental processing time for yellow color is more than red and green.
PMCID: PMC4280496  PMID: 25580294
21.  Protective Association of Tumor Necrosis Factor Superfamily 15 (TNFSF15) Polymorphic Haplotype with Ulcerative Colitis and Crohn's Disease in an Indian Population 
PLoS ONE  2014;9(12):e114665.
Tumor necrosis factor superfamily (TNFSF) proteins are involved in the genesis of inflammatory bowel disease (IBD). We examined the association of seven single nucleotide polymorphisms (SNP) in the TNFSF15 gene with Crohn's disease (CD) and ulcerative colitis (UC) in the Indian population.
Seven SNPs in the TNFSF15 gene (rs10114470, rs3810936, rs6478108, rs4263839, rs6478109, rs7848647 and rs7869487) were genotyped in 309 CD patients, 330 UC patients and 437 healthy controls using the Sequenom iPLEX MassArray platform. Disease associations were evaluated for allelotypes and for genotypes.
The minor T alleles and the TT genotypes of rs10114470 and rs3810936 were significantly protectively associated with both CD and UC. The CC genotype of rs6478108, AA genotype of rs4263839, the AA genotype of rs6478109, the TT genotype of rs7848647 and the CC genotype of rs7869487 were all protectively associated with CD but not with UC. Two haplotype blocks could be discerned, one where SNPs rs10114470 and rs3810936 were in tight LD (D′ = 0.8) and the other where rs6478108, rs4263839, rs6478109, rs7848647 and rs7869487 were in tight LD (D′ 0.92–1.00). The second block of haplotypes were not associated with CD or with UC. The first block of haplotypes was very significantly associated with both CD and UC.
Strong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population.
PMCID: PMC4264777  PMID: 25501099
22.  Regulation of Mcl-1 Expression in Context to Bone Marrow Stromal Microenvironment in Chronic Lymphocytic Leukemia1 
Neoplasia (New York, N.Y.)  2014;16(12):1036-1046.
A growing body of evidence suggests that the resistance of CLL cells to apoptosis is partly mediated through the interactions between leukemia cells and adjacent stromal cells residing in the lymphatic tissue or bone marrow microenvironment. Mcl-1, an anti-apoptotic protein that is associated with failure to treatment is up-regulated in CLL lymphocytes after interaction with microenvironment. However, the regulation of its expression in context to microenvironment is unclear. We evaluated and compared changes in Mcl-1 in CLL B-cells in suspension culture and when co-cultured on stromal cells. The blockade of apoptosis in co-cultured CLL cells is associated with diminution in caspase-3 and PARP cleavage and is not dependent on cytogenetic profile or prognostic factors of the disease. Stroma-derived resistance to apoptosis is associated with a cascade of transcriptional events such as increase in levels of total RNA Pol II and its phosphorylation at Ser2 and Ser5, increase in the rate of global RNA synthesis, and amplification of Mcl-1 transcript levels. The latter is associated with increase in Mcl-1 protein level without an impact on the levels of Bcl-2 and Bcl-xL. Post-translational modifications of protein kinases show increased phosphorylation of Akt at Ser473, Erk at Thr202/Tyr204 and Gsk-3β at Ser9 and augmentation of total Mcl-1 accumulation along with phosphorylation at Ser159/Thr163 sites. Collectively, stroma-induced apoptosis resistance is mediated through signaling proteins that regulate transcriptional and translational expression and post-translational modification of Mcl-1 in CLL cells in context to bone marrow stromal microenvironment.
PMCID: PMC4309260  PMID: 25499217
23.  Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 
Kassebaum, Nicholas J | Bertozzi-Villa, Amelia | Coggeshall, Megan S | Shackelford, Katya A | Steiner, Caitlyn | Heuton, Kyle R | Gonzalez-Medina, Diego | Barber, Ryan | Huynh, Chantal | Dicker, Daniel | Templin, Tara | Wolock, Timothy M | Ozgoren, Ayse Abbasoglu | Abd-Allah, Foad | Abera, Semaw Ferede | Abubakar, Ibrahim | Achoki, Tom | Adelekan, Ademola | Ademi, Zanfina | Adou, Arsène Kouablan | Adsuar, José C | Agardh, Emilie E | Akena, Dickens | Alasfoor, Deena | Alemu, Zewdie Aderaw | Alfonso-Cristancho, Rafael | Alhabib, Samia | Ali, Raghib | Al Kahbouri, Mazin J | Alla, François | Allen, Peter J | AlMazroa, Mohammad A | Alsharif, Ubai | Alvarez, Elena | Alvis-Guzmán, Nelson | Amankwaa, Adansi A | Amare, Azmeraw T | Amini, Hassan | Ammar, Walid | Antonio, Carl A T | Anwari, Palwasha | Ärnlöv, Johan | Arsenijevic, Valentina S Arsic | Artaman, Ali | Asad, Majed Masoud | Asghar, Rana J | Assadi, Reza | Atkins, Lydia S | Badawi, Alaa | Balakrishnan, Kalpana | Basu, Arindam | Basu, Sanjay | Beardsley, Justin | Bedi, Neeraj | Bekele, Tolesa | Bell, Michelle L | Bernabe, Eduardo | Beyene, Tariku J | Bhutta, Zulfiqar | Abdulhak, Aref Bin | Blore, Jed D | Basara, Berrak Bora | Bose, Dipan | Breitborde, Nicholas | Cárdenas, Rosario | Castañeda-Orjuela, Carlos A | Castro, Ruben Estanislao | Catalá-López, Ferrán | Cavlin, Alanur | Chang, Jung-Chen | Che, Xuan | Christophi, Costas A | Chugh, Sumeet S | Cirillo, Massimo | Colquhoun, Samantha M | Cooper, Leslie Trumbull | Cooper, Cyrus | da Costa Leite, Iuri | Dandona, Lalit | Dandona, Rakhi | Davis, Adrian | Dayama, Anand | Degenhardt, Louisa | De Leo, Diego | del Pozo-Cruz, Borja | Deribe, Kebede | Dessalegn, Muluken | deVeber, Gabrielle A | Dharmaratne, Samath D | Dilmen, Uğur | Ding, Eric L | Dorrington, Rob E | Driscoll, Tim R | Ermakov, Sergei Petrovich | Esteghamati, Alireza | Faraon, Emerito Jose A | Farzadfar, Farshad | Felicio, Manuela Mendonca | Fereshtehnejad, Seyed-Mohammad | de Lima, Graça Maria Ferreira | Forouzanfar, Mohammad H | França, Elisabeth B | Gaffikin, Lynne | Gambashidze, Ketevan | Gankpé, Fortuné Gbètoho | Garcia, Ana C | Geleijnse, Johanna M | Gibney, Katherine B | Giroud, Maurice | Glaser, Elizabeth L | Goginashvili, Ketevan | Gona, Philimon | González-Castell, Dinorah | Goto, Atsushi | Gouda, Hebe N | Gugnani, Harish Chander | Gupta, Rahul | Gupta, Rajeev | Hafezi-Nejad, Nima | Hamadeh, Randah Ribhi | Hammami, Mouhanad | Hankey, Graeme J | Harb, Hilda L | Havmoeller, Rasmus | Hay, Simon I | Heredia Pi, Ileana B | Hoek, Hans W | Hosgood, H Dean | Hoy, Damian G | Husseini, Abdullatif | Idrisov, Bulat T | Innos, Kaire | Inoue, Manami | Jacobsen, Kathryn H | Jahangir, Eiman | Jee, Sun Ha | Jensen, Paul N | Jha, Vivekanand | Jiang, Guohong | Jonas, Jost B | Juel, Knud | Kabagambe, Edmond Kato | Kan, Haidong | Karam, Nadim E | Karch, André | Karema, Corine Kakizi | Kaul, Anil | Kawakami, Norito | Kazanjan, Konstantin | Kazi, Dhruv S | Kemp, Andrew H | Kengne, Andre Pascal | Kereselidze, Maia | Khader, Yousef Saleh | Khalifa, Shams Eldin Ali Hassan | Khan, Ejaz Ahmed | Khang, Young-Ho | Knibbs, Luke | Kokubo, Yoshihiro | Kosen, Soewarta | Defo, Barthelemy Kuate | Kulkarni, Chanda | Kulkarni, Veena S | Kumar, G Anil | Kumar, Kaushalendra | Kumar, Ravi B | Kwan, Gene | Lai, Taavi | Lalloo, Ratilal | Lam, Hilton | Lansingh, Van C | Larsson, Anders | Lee, Jong-Tae | Leigh, James | Leinsalu, Mall | Leung, Ricky | Li, Xiaohong | Li, Yichong | Li, Yongmei | Liang, Juan | Liang, Xiaofeng | Lim, Stephen S | Lin, Hsien-Ho | Lipshultz, Steven E | Liu, Shiwei | Liu, Yang | Lloyd, Belinda K | London, Stephanie J | Lotufo, Paulo A | Ma, Jixiang | Ma, Stefan | Machado, Vasco Manuel Pedro | Mainoo, Nana Kwaku | Majdan, Marek | Mapoma, Christopher Chabila | Marcenes, Wagner | Marzan, Melvin Barrientos | Mason-Jones, Amanda J | Mehndiratta, Man Mohan | Mejia-Rodriguez, Fabiola | Memish, Ziad A | Mendoza, Walter | Miller, Ted R | Mills, Edward J | Mokdad, Ali H | Mola, Glen Liddell | Monasta, Lorenzo | de la Cruz Monis, Jonathan | Hernandez, Julio Cesar Montañez | Moore, Ami R | Moradi-Lakeh, Maziar | Mori, Rintaro | Mueller, Ulrich O | Mukaigawara, Mitsuru | Naheed, Aliya | Naidoo, Kovin S | Nand, Devina | Nangia, Vinay | Nash, Denis | Nejjari, Chakib | Nelson, Robert G | Neupane, Sudan Prasad | Newton, Charles R | Ng, Marie | Nieuwenhuijsen, Mark J | Nisar, Muhammad Imran | Nolte, Sandra | Norheim, Ole F | Nyakarahuka, Luke | Oh, In-Hwan | Ohkubo, Takayoshi | Olusanya, Bolajoko O | Omer, Saad B | Opio, John Nelson | Orisakwe, Orish Ebere | Pandian, Jeyaraj D | Papachristou, Christina | Park, Jae-Hyun | Caicedo, Angel J Paternina | Patten, Scott B | Paul, Vinod K | Pavlin, Boris Igor | Pearce, Neil | Pereira, David M | Pesudovs, Konrad | Petzold, Max | Poenaru, Dan | Polanczyk, Guilherme V | Polinder, Suzanne | Pope, Dan | Pourmalek, Farshad | Qato, Dima | Quistberg, D Alex | Rafay, Anwar | Rahimi, Kazem | Rahimi-Movaghar, Vafa | Rahman, Sajjad ur | Raju, Murugesan | Rana, Saleem M | Refaat, Amany | Ronfani, Luca | Roy, Nobhojit | Sánchez Pimienta, Tania Georgina | Sahraian, Mohammad Ali | Salomon, Joshua A | Sampson, Uchechukwu | Santos, Itamar S | Sawhney, Monika | Sayinzoga, Felix | Schneider, Ione J C | Schumacher, Austin | Schwebel, David C | Seedat, Soraya | Sepanlou, Sadaf G | Servan-Mori, Edson E | Shakh-Nazarova, Marina | Sheikhbahaei, Sara | Shibuya, Kenji | Shin, Hwashin Hyun | Shiue, Ivy | Sigfusdottir, Inga Dora | Silberberg, Donald H | Silva, Andrea P | Singh, Jasvinder A | Skirbekk, Vegard | Sliwa, Karen | Soshnikov, Sergey S | Sposato, Luciano A | Sreeramareddy, Chandrashekhar T | Stroumpoulis, Konstantinos | Sturua, Lela | Sykes, Bryan L | Tabb, Karen M | Talongwa, Roberto Tchio | Tan, Feng | Teixeira, Carolina Maria | Tenkorang, Eric Yeboah | Terkawi, Abdullah Sulieman | Thorne-Lyman, Andrew L | Tirschwell, David L | Towbin, Jeffrey A | Tran, Bach X | Tsilimbaris, Miltiadis | Uchendu, Uche S | Ukwaja, Kingsley N | Undurraga, Eduardo A | Uzun, Selen Begüm | Vallely, Andrew J | van Gool, Coen H | Vasankari, Tommi J | Vavilala, Monica S | Venketasubramanian, N | Villalpando, Salvador | Violante, Francesco S | Vlassov, Vasiliy Victorovich | Vos, Theo | Waller, Stephen | Wang, Haidong | Wang, Linhong | Wang, XiaoRong | Wang, Yanping | Weichenthal, Scott | Weiderpass, Elisabete | Weintraub, Robert G | Westerman, Ronny | Wilkinson, James D | Woldeyohannes, Solomon Meseret | Wong, John Q | Wordofa, Muluemebet Abera | Xu, Gelin | Yang, Yang C | Yano, Yuichiro | Yentur, Gokalp Kadri | Yip, Paul | Yonemoto, Naohiro | Yoon, Seok-Jun | Younis, Mustafa Z | Yu, Chuanhua | Jin, Kim Yun | El SayedZaki, Maysaa | Zhao, Yong | Zheng, Yingfeng | Zhou, Maigeng | Zhu, Jun | Zou, Xiao Nong | Lopez, Alan D | Naghavi, Mohsen | Murray, Christopher J L | Lozano, Rafael
Lancet  2014;384(9947):980-1004.
The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100 000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990–2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.
292 982 (95% UI 261 017–327 792) maternal deaths occurred in 2013, compared with 376 034 (343 483–407 574) in 1990. The global annual rate of change in the MMR was −0·3% (−1·1 to 0·6) from 1990 to 2003, and −2·7% (−3·9 to −1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290–2866) maternal deaths were related to HIV in 2013, 0·4% (0·2–0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1–1262·8) in South Sudan to 2·4 (1·6–3·6) in Iceland.
Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.
Bill & Melinda Gates Foundation.
PMCID: PMC4255481  PMID: 24797575
24.  Photolytic Labeling to Probe Molecular Interactions in Lyophilized Powders 
Molecular pharmaceutics  2013;10(12):4629-4639.
Local side-chain interactions in lyophilized protein formulations were mapped using solid-state photolytic labeling-mass spectrometry (ssPL-MS). Photoactive amino acid analogs (PAAs) were used as probes and either added to the lyophilized matrix or incorporated within the amino acid sequence of a peptide. In the first approach, apomyoglobin was lyophilized with sucrose and varying concentrations of photo-leucine (L-2-amino-4, 4′-azipentanoic acid; pLeu). The lyophilized solid was irradiated at 365 nm to initiate photolabeling. The rate and extent of labeling were measured using ESI-HPLC-MS, with labeling reaching a plateau at ∼ 30 min, forming up to 6 labeled populations. Bottom-up MS/MS analysis was able to provide peptidelevel resolution of the location of pLeu. ssPL-MS was also able to detect differences in side-chain environment between sucrose and guanidine hydrochloride formulations. In the second approach, peptide GCG (1-8)* containing p-benzoyl-L-phenylalanine (pBpA) in the amino acid sequence was lyophilized with various excipients and irradiated. Peptide-peptide and peptide-excipient adducts were detected using MS. Top-down MS/MS on the peptide dimer provided amino acidlevel resolution regarding interactions and the cross-linking partner for pBpA in the solid state. The results show that ssPL-MS can provide high-resolution information about protein interactions in the lyophilized environment.
PMCID: PMC3913734  PMID: 24125175
Photolytic labeling; mass spectrometry; lyophilized formulations; protein-protein interactions; apomyoglobin; photo-leucine; p-benzoyl-L-phenylalanine
25.  Nanoparticles for localized delivery of hyaluronan oligomers (HA-o) towards regenerative repair of elastic matrix 
Acta biomaterialia  2013;9(12):9292-9302.
Abdominal aortic aneurysms (AAAs) are rupture-prone progressive dilations of the infrarenal aorta due to a loss of elastic matrix that lead to weakening of the aortic wall. Therapies to coax biomimetic regenerative repair of the elastic matrix by resident, diseased vascular cells may thus be useful to slow, arrest, or regress AAA growth. Hyaluronan oligomers (HA-o) have been shown to induce elastic matrix synthesis by healthy and aneurysmal rat aortic smooth muscle cells (SMCs) in vitro but only via exogenous dosing, which potentially has side effects and limitations to in vivo delivery towards therapy. In this paper, we describe the development of HA-o loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for targeted, controlled, and sustained delivery of HA-o towards the elastogenic induction of aneurysmal rat aortic SMCs. These NPs were able to deliver HA-o over an extended period (>30 days) at previously determined elastogenic doses (0.2 – 20 μg/mL). HA-o released from the NPs led to dose dependent increases in elastic matrix synthesis, and the recruitment and activity of lysyl oxidase (LOX), the enzyme which crosslinks elastin precursor molecules into mature fibers/matrix. Therefore, we were able to successfully develop a nanoparticle based system for controlled and sustained HA-o delivery for the in vitro elastogenic induction of aneurysmal rat aortic smooth muscle cells (EaRASMCs).
PMCID: PMC4024830  PMID: 23917150
Nanoparticles; drug delivery; elastic matrix; regenerative matrix repair; hyaluronan oligomers

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