Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008-2018.

OBJECTIVES: World Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process. STUDY DESIGN: We did a systematic, retrospective analysis of research questions identified in the published guidelines. METHODS: We analyzed guidelines published between January 1, 2008, and December 31, 2018, by the Communicable Diseases Cluster in five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs). Research questions were extracted independently by two researchers. We analyzed the distribution of research questions by disease and by topic category and did a qualitative assessment of optimum practice for research question generation during the guideline development process. RESULTS: A total of 48 guidelines were included: 26 on HIV, 1 on malaria, 11 on TB, 5 on TB/HIV, and 5 on NTDs. Overall, 36 (75%) guidelines encompassed a total of 360 explicit research questions; the remainder did not contain specific research questions. The number of research questions that focused on TB was 49, TB/HIV was 38, HIV was 250, and NTDs was 23. The number of research questions that focused on diagnosis was 43 (11.9%) of 360, prevention was 62 (17.2%), treatment was 103 (28.6%), good practice was 12 (3.3%), service delivery was 86 (23.8%), and other areas was 54 (15%). Research questions were often not formulated in a specific or actionable way and were hard to identify in the guideline. Examples of good practice identified by the review team involved the generation of specific and narrowly defined research questions, with accompanying recommendations for appropriate study design. CONCLUSIONS: The WHO must strengthen its approach to identifying and presenting research questions during the guideline development process. Ensuring access to research questions is a key next step in adding value to the guideline development process.

A Standard Mutual Authentication Protocol for Cloud Computing Based Health Care System.

Telecare Medical Information System (TMIS) supports a standard platform to the patient for getting necessary medical treatment from the doctor(s) via Internet communication. Security protection is important for medical records (data) of the patients because of very sensitive information. Besides, patient anonymity is another most important property, which must be protected. Most recently, Chiou et al. suggested an authentication protocol for TMIS by utilizing the concept of cloud environment. They claimed that their protocol is patient anonymous and well security protected. We reviewed their protocol and found that it is completely insecure against patient anonymity. Further, the same protocol is not protected against mobile device stolen attack. In order to improve security level and complexity, we design a light weight authentication protocol for the same environment. Our security analysis ensures resilience of all possible security attacks. The performance of our protocol is relatively standard in comparison with the related previous research.

A novel user authentication and key agreement protocol for accessing multi-medical server usable in TMIS.

Telecare Medical Information System (TMIS) makes an efficient and convenient connection between patient(s)/user(s) at home and doctor(s) at a clinical center. To ensure secure connection between the two entities (patient(s)/user(s), doctor(s)), user authentication is enormously important for the medical server. In this regard, many authentication protocols have been proposed in the literature only for accessing single medical server. In order to fix the drawbacks of the single medical server, we have primarily developed a novel architecture for accessing several medical services of the multi-medical server, where a user can directly communicate with the doctor of the medical server securely. Thereafter, we have developed a smart card based user authentication and key agreement security protocol usable for TMIS system using cryptographic one-way hash function. We have analyzed the security of our proposed authentication scheme through both formal and informal security analysis. Furthermore, we have simulated the proposed scheme for the formal security verification using the widely-accepted AVISPA (Automated Validation of Internet Security Protocols and Applications) tool and showed that the scheme is secure against the replay and man-in-the-middle attacks. The informal security analysis is also presented which confirms that the protocol has well security protection on the relevant security attacks. The security and performance comparison analysis confirm that the proposed protocol not only provides security protection on the above mentioned attacks, but it also achieves better complexities along with efficient login and password change phase.

A Secure Three-Factor User Authentication and Key Agreement Protocol for TMIS With User Anonymity.

Telecare medical information system (TMIS) makes an efficient and convenient connection between patient(s)/user(s) and doctor(s) over the insecure internet. Therefore, data security, privacy and user authentication are enormously important for accessing important medical data over insecure communication. Recently, many user authentication protocols for TMIS have been proposed in the literature and it has been observed that most of the protocols cannot achieve complete security requirements. In this paper, we have scrutinized two (Mishra et al., Xu et al.) remote user authentication protocols using smart card and explained that both the protocols are suffering against several security weaknesses. We have then presented three-factor user authentication and key agreement protocol usable for TMIS, which fix the security pitfalls of the above mentioned schemes. The informal cryptanalysis makes certain that the proposed protocol provides well security protection on the relevant security attacks. Furthermore, the simulator AVISPA tool confirms that the protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. The security functionalities and performance comparison analysis confirm that our protocol not only provide strong protection on security attacks, but it also achieves better complexities along with efficient login and password change phase as well as session key verification property.

An Improved RSA Based User Authentication and Session Key Agreement Protocol Usable in TMIS.

Recently, Giri et al.'s proposed a RSA cryptosystem based remote user authentication scheme for telecare medical information system and claimed that the protocol is secure against all the relevant security attacks. However, we have scrutinized the Giri et al.'s protocol and pointed out that the protocol is not secure against off-line password guessing attack, privileged insider attack and also suffers from anonymity problem. Moreover, the extension of password guessing attack leads to more security weaknesses. Therefore, this protocol needs improvement in terms of security before implementing in real-life application. To fix the mentioned security pitfalls, this paper proposes an improved scheme over Giri et al.'s scheme, which preserves user anonymity property. We have then simulated the proposed protocol using widely-accepted AVISPA tool which ensures that the protocol is SAFE under OFMC and CL-AtSe models, that means the same protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. The informal cryptanalysis has been also presented, which confirmed that the proposed protocol provides well security protection on the relevant security attacks. The performance analysis section compares the proposed protocol with other existing protocols in terms of security and it has been observed that the protocol provides more security and achieves additional functionalities such as user anonymity and session key verification.

An Efficient and Practical Smart Card Based Anonymity Preserving User Authentication Scheme for TMIS using Elliptic Curve Cryptography.

In the last few years, numerous remote user authentication and session key agreement schemes have been put forwarded for Telecare Medical Information System, where the patient and medical server exchange medical information using Internet. We have found that most of the schemes are not usable for practical applications due to known security weaknesses. It is also worth to note that unrestricted number of patients login to the single medical server across the globe. Therefore, the computation and maintenance overhead would be high and the server may fail to provide services. In this article, we have designed a medical system architecture and a standard mutual authentication scheme for single medical server, where the patient can securely exchange medical data with the doctor(s) via trusted central medical server over any insecure network. We then explored the security of the scheme with its resilience to attacks. Moreover, we formally validated the proposed scheme through the simulation using Automated Validation of Internet Security Schemes and Applications software whose outcomes confirm that the scheme is protected against active and passive attacks. The performance comparison demonstrated that the proposed scheme has lower communication cost than the existing schemes in literature. In addition, the computation cost of the proposed scheme is nearly equal to the exiting schemes. The proposed scheme not only efficient in terms of different security attacks, but it also provides an efficient login, mutual authentication, session key agreement and verification and password update phases along with password recovery.

Cryptanalysis and Enhancement of Anonymity Preserving Remote User Mutual Authentication and Session Key Agreement Scheme for E-Health Care Systems.

The E-health care systems employ IT infrastructure for maximizing health care resources utilization as well as providing flexible opportunities to the remote patient. Therefore, transmission of medical data over any public networks is necessary in health care system. Note that patient authentication including secure data transmission in e-health care system is critical issue. Although several user authentication schemes for accessing remote services are available, their security analysis show that none of them are free from relevant security attacks. We reviewed Das et al.'s scheme and demonstrated their scheme lacks proper protection against several security attacks such as user anonymity, off-line password guessing attack, smart card theft attack, user impersonation attack, server impersonation attack, session key discloser attack. In order to overcome the mentioned security pitfalls, this paper proposes an anonymity preserving remote patient authentication scheme usable in E-health care systems. We then validated the security of the proposed scheme using BAN logic that ensures secure mutual authentication and session key agreement. We also presented the experimental results of the proposed scheme using AVISPA software and the results ensure that our scheme is secure under OFMC and CL-AtSe models. Moreover, resilience of relevant security attacks has been proved through both formal and informal security analysis. The performance analysis and comparison with other schemes are also made, and it has been found that the proposed scheme overcomes the security drawbacks of the Das et al.'s scheme and additionally achieves extra security requirements.

Design and Analysis of an Enhanced Patient-Server Mutual Authentication Protocol for Telecare Medical Information System.

In order to access remote medical server, generally the patients utilize smart card to login to the server. It has been observed that most of the user (patient) authentication protocols suffer from smart card stolen attack that means the attacker can mount several common attacks after extracting smart card information. Recently, Lu et al.'s proposes a session key agreement protocol between the patient and remote medical server and claims that the same protocol is secure against relevant security attacks. However, this paper presents several security attacks on Lu et al.'s protocol such as identity trace attack, new smart card issue attack, patient impersonation attack and medical server impersonation attack. In order to fix the mentioned security pitfalls including smart card stolen attack, this paper proposes an efficient remote mutual authentication protocol using smart card. We have then simulated the proposed protocol using widely-accepted AVISPA simulation tool whose results make certain that the same protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. Moreover, the rigorous security analysis proves that the proposed protocol provides strong security protection on the relevant security attacks including smart card stolen attack. We compare the proposed scheme with several related schemes in terms of computation cost and communication cost as well as security functionalities. It has been observed that the proposed scheme is comparatively better than related existing schemes.

ERRß signalling through FST and BCAS2 inhibits cellular proliferation in breast cancer cells.

BACKGROUND: The overexpression of oestrogen-related receptor-ß (ERRß) in breast cancer patients is correlated with improved prognosis and longer relapse-free survival, and the level of ERRß mRNA is inversely correlated with the S-phase fraction of cells from breast cancer patients. METHODS: Chromatin immunoprecipitation (ChIP) cloning of ERRß transcriptional targets and gel supershift assays identified breast cancer amplified sequence 2 (BCAS2) and Follistatin (FST) as two important downstream genes that help to regulate tumourigenesis. Confocal microscopy, co-immunoprecipitation (CoIP), western blotting and quantitative real-time PCR confirmed the involvement of ERRß in oestrogen signalling. RESULTS: Overexpressed ERRß induced FST-mediated apoptosis in breast cancer cells, and E-cadherin expression was also enhanced through upregulation of FST. However, this anti-proliferative signalling function was challenged by ERRß-mediated BCAS2 upregulation, which inhibited FST transcription through the downregulation of ß-catenin/TCF4 recruitment to the FST promoter. Interestingly, ERRß-mediated upregulation of BCAS2 downregulated the major G1-S transition marker cyclin D1, despite the predictable oncogenic properties of BCAS2. INTERPRETATION: Our study provides the first evidence that ERRß, which is a coregulator of ERα also acts as a potential tumour-suppressor molecule in breast cancer. Our current report also provides novel insights into the entire cascade of ERRß signalling events, which may lead to BCAS2-mediated blockage of the G1/S transition and inhibition of the epithelial to mesenchymal transition through FST-mediated regulation of E-cadherin. Importantly, matrix metalloprotease 7, which is a classical mediator of metastasis and E-cadherin cleavage, was also restricted as a result of ERRß-mediated FST overexpression.

Cytokine responses in the Japanese pufferfish (Takifugu rubripes) head kidney cells induced with heat-killed probiotics isolated from the Mongolian dairy products.

Cytokine responses in the Japanese pufferfish (Takifugu rubripes) head kidney (HK) cells to heat-killed lactic acid bacteria probiotics isolated from the Mongolian dairy products were investigated by transcriptomic examination. The HK cells were incubated with two heat-killed bacteria, namely Lactobacillus paracasei spp. paracasei (strain 06TCa22) and L. plantarum (strain 06CC2) and the responses of 16 cytokine genes at 0 (control), 1, 4, 8, 12, 24 and 48 h post-stimulation were assayed by multiplex RT-PCR analysis (GenomeLab Genetic Analysis System, GeXPS; Beckman Coulter, Inc.). The 16 genes included in the assay were pro-inflammatory cytokines (IL-1ß, IL-6, IL-17A/F-3, TNF-α and TNF-N), cell-mediated immune regulators (IL-12p35, IL-12p40 and IL-18), antiviral (I-IFN-1 and IFN-γ) and other regulatory (IL-2, IL-7, IL-15, IL-21, IL-10 and TGF-ß1) cytokines. Despite the differences in the transcriptional profiles, expression of all the cytokines tested here was significantly elevated by both the probiotic bacterial stimulants compared with the unstimulated control. Therefore, this in vitro study has demonstrated the modulation of cytokine defense mechanisms in the HK cells by the two heat-killed probiotics indicating their potentiality as novel immunostimulants to fish. However, strain-dependent varied expression of important cytokines (cell-mediated immune regulators, antiviral and anti-inflammatory cytokines) suggests better efficacy of L. paracasei spp. paracasei strain as fish immunostimulant. Further in vivo studies to elucidate the cytokine regulation networks will validate our present observations. A careful evaluation of ant-inflammatory properties may be undertaken using single strain to affirm the immunostimulatory capability. Moreover, application timings and frequency to assess the longevity of immunostimulant effects and to make the application cost-effective need to be evaluated before any practical use in aquaculture.

Elevated cytokine responses to Vibrio harveyi infection in the Japanese pufferfish (Takifugu rubripes) treated with Lactobacillus paracasei spp. paracasei (06TCa22) isolated from the Mongolian dairy product.

With the aim of evaluating the effect of a Mongolian dairy product derived Lactobacillus paracasei spp. paracasei (strain 06TCa22) (Lpp) on the cytokine-mediated immune responses to Vibrio harveyi infection, we examined 16 cytokine expressions in the Japanese pufferfish, Takifugu rubripes. Fish were orally treated with the heat-killed Lpp at 1 mg g(-1) body weight d(-1) for 3 days. At 24 h posttreatment, fish were infected by an intramuscular injection of 0.1 mL V. harveyi bacterial suspension (10(8) cfu mL(-1)). Additionally, superoxide anion production (SAP) and phagocytic activity (PA) of head kidney cells were assessed during 120 h postinfection period. Significant up-regulation of pro-inflammatory (IL-1ß, IL-6, IL-17A/F-3, TNF-α and TNF-N), cell-mediated immune inducing (IL-12p35, IL-12p40 and IL-18), antiviral/intra-cellular pathogen killing (I-IFN-1 and IFN-γ), anti-inflammatory (IL-10) and lymphocyte agonistic (IL-2, IL-7, IL-15, IL-21 and TGF-ß1) cytokines was observed in the treated fish compared to control ones during the pathogen infection. Furthermore, significantly increased SAP and PA (P < 0.01; 0.05) were recorded in the treated fish compared to untreated fish. These results suggest the beneficial role of Lpp in enhancement of cytokine-mediated immunity in the Japanese pufferfish against V. harveyi infection and application of this product as a potential fish immunostimulant.

Parathyroid failure following thyroid surgery.

This cross-sectional study was done to see the association of post thyroidectomy parathyroid failure with thyroid disease and type of surgery. It was carried out in the Department of Otolaryngology-Head and Neck Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka during the period of July 2008 to June 2010. Total 50 cases of thyroid malignancy and multinodular goiter who had undergone total or near total thyroidectomy with or without neck dissection were studied. In this study highest number of cases were found in 3rd decade of age (28%) and there was female predominance (M:F=1:3.54). Overall frequency of post operative hypocalcaemia was 30% (26% was temporary hypocalcaemia and 4% was permanent). Hypocalcaemia revealed clinically in 20% cases and remained subclinical in 10% cases. Hypocalcaemia developed in 42.30% cases of malignant thyroid disease and 16.66% cases of benign thyroid disease (p<0.05). It was found in 54.54% cases with neck dissection and 23.07% cases without neck dissection (p<0.05). Hypocalcaemia developed in 62.5% cases where parathyroid gland were not identified and 23.8% cases where parathyroid gland was identified. Hypocalcaemia developed most commonly on the 2nd post operative day (73.33%). There is a significance difference with development of parathyroid failure after thyroid surgery between benign and malignant thyroid disease and also between thyroid surgery with or without neck dissection.

Gonad recrudescence and annual sex steroid patterns in female goldspot mullet, Liza parsia reared in brackishwater pond.

Goldspot mullet, Liza parsia is a commercially important fish of South East Asia, where its farming depends on wild seed resources due to unavailability of hatchery technology. It, therefore, is important to understand the annual reproductive cycle of female L. parsia in captivity. In this study, adult male and female L. parsia (body weight ranges: 45-90 g; total length ranges: 100-125 mm, age >1 year) were collected from the wild and reared in a brackishwater pond. Thereafter, fish were randomly sampled at monthly intervals to measure the hepatosomatic index (HSI), gonadosomatic index (GSI), levels of serum steroids (testosterone, T; 17ß-estradiol, E2 and 17α-hydroxyprogesterone, 17-OHP), and oocyte growth. Results exhibited that female L. parsia undergoes six different maturation stages, namely I (oocyte diameter, OD: <100 µm), II (OD: 100-350 µm), III (OD: 350-400 µm), IV (vitellogenic oocyte, OD: 400-450 µm), V (ripe oocyte, OD: 450-550 µm) and VI (atretic oocyte, OD: 60-150 µm), with synchronous oocyte development. The highest (P < 0.05) HSI (1.96 ± 0.24) and GSI (12.01 ± 0.73) were recorded in December and January, respectively. Concentration of E2 gradually increased from August and reached its peak (807.67 ± 25.98 pg mL-1, P < 0.05) in December. The level of 17-OHP (85.87 ± 0.91 pg mL-1) was at its peak during the normal spawning month (January) (P < 0.05). Overall, the results indicated that L. parsia attains maturity in brackishwater pond, which is consistent with previous observations, and altogether provide the basis to develop a breeding technology in captivity through hormonal and environmental manipulations.

Exploration of binding mechanism of triclosan towards cancer markers using molecular docking and molecular dynamics.

The molecule 5-chloro-2-(2,4-dichlorophenoxy) phenol is well-known as Triclosan (TCS), which is also a potential endocrine disrupting synthetic chemical. TCS exposure has been connected to the control of the human enoyl-acyl carrier protein-reductase (hER), which has been linked to a range of life threatening diseases. However, other than hER, the new protein targets for TCS that are responsible for a variety of cancers are yet unclear. The goal of this work is to investigate into the protein binding patterns of TCS and proteins from various cancer signaling pathways. Discovery Studio 4.1 was used to perform molecular docking and molecular dynamics (MD) on the protein-triclosan complex. The proteins were first screened using CHARMM-based docking with a CDOCKER energy greater than -21.40 kcal/mol. The CDOCKER energies of Fas-associated death domain (FADD), Receptor-interacting protein 1 (RIP1), F-κB-inducing kinase (NIK), c-Jun N-terminal kinase (JNK), Apoptosis signal-regulating kinase 1 (ASK1), B-cell lymphoma 2 (Bcl-2), Apoptosis-inducing factor (AIF), α-tubulin, and Actin were -20.68 kcal/mol, -26.88 kcal/mol, -23.43 kcal/mol, -22.21 kcal/mol, -20.40 kcal/mol, -21.10 kcal/mol, -20.98 kcal/mol, -24.67 kcal/mol, and -23.09 kcal/mol respectively. MD was performed on the screened proteins by standard dynamics cascade tool using CHARMM Force field. The MD results were accessed using the energy-time graph, root-mean-square deviation (RMSD), and root mean square fluctuations (RMSF). The 100 conformers of α-tubulin, NIK, FADD, and RIP1 were found to have a trend of increasing RMSD, whereas Bcl-2, ASK1, AIF, Actin, and JNK proteins had lower RMSD values. In compared to FADD, AIF, and JNK, the RMSF variations of the Bcl-2, ASK1, α-tubulin, Actin, NIK, and RIP1 residues were shown to be high. Similar patterns were seen in the energy variations, which range from 1000 kcal/mol to 2000 kcal/mol. RIP1 and Bcl-2 showed more variation in the sidechain RMSF in comparison to FADD, ASK1, AIF, Actin, α-tubulin, NIK and JNK. Thus, it can be postulated that AIF and JNK proteins of apoptosis signaling pathway are pivotal in the TCS mediated reactions.

A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis.

Nucleoplasmic calcium ions (Ca2+) influence nuclear functions as critical as gene transcription, apoptosis, DNA repair, topoisomerase activation and polymerase unfolding. Although both inositol trisphosphate receptors and ryanodine receptors, types of Ca2+ channel, are present in the nuclear membrane, their role in the homeostasis of nuclear Ca2+ remains unclear. Here we report the existence in the inner nuclear membrane of a functionally active CD38/ADP-ribosyl cyclase that has its catalytic site within the nucleoplasm. We propose that the enzyme catalyses the intranuclear cyclization of nicotinamide adenine dinucleotide to cyclic adenosine diphosphate ribose. The latter activates ryanodine receptors of the inner nuclear membrane to trigger nucleoplasmic Ca2+ release.

Targeting of NH2-terminal-processed microsomal protein to mitochondria: a novel pathway for the biogenesis of hepatic mitochondrial P450MT2.

Cytochrome P4501A1 is a hepatic, microsomal membrane-bound enzyme that is highly induced by various xenobiotic agents. Two NH2-terminal truncated forms of this P450, termed P450MT2a and MT2b, are also found localized in mitochondria from beta-naphthoflavone-induced livers. In this paper, we demonstrate that P4501A1 has a chimeric NH2-terminal signal that facilitates the targeting of the protein to both the ER and mitochondria. The NH2-terminal 30-amino acid stretch of P4501A1 is thought to provide signals for ER membrane insertion and also stop transfer. The present study provides evidence that a sequence motif immediately COOH-terminal (residues 33-44) to the transmembrane domain functions as a mitochondrial targeting signal under both in vivo and in vitro conditions, and that the positively charged residues at positions 34 and 39 are critical for mitochondrial targeting. Results suggest that 25% of P4501A1 nascent chains, which escape ER membrane insertion, are processed by a liver cytosolic endoprotease. We postulate that the NH2-terminal proteolytic cleavage activates a cryptic mitochondrial targeting signal. Immunofluorescence microscopy showed that a portion of transiently expressed P4501A1 is colocalized with the mitochondrial-specific marker protein cytochrome oxidase subunit I. The mitochondrial-associated MT2a and MT2b are localized within the inner membrane compartment, as tested by resistance to limited proteolysis in both intact mitochondria and mitoplasts. Our results therefore describe a novel mechanism whereby proteins with chimeric signal sequence are targeted to the ER as well as to the mitochondria.

CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption.

The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca(2+) release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD(+) surrogate, NGD(+), to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD(+)) triggered a cytosolic Ca(2+) signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca(2+) change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr.

Conjugal transfer of the gonococcal penicillinase plasmid.

Certain gonococci, which heretofore have lacked a conjugal mating system, can sexually transfer a small plasmid (4.5 x 10)6) daltons) which carries the gene for beta-lactamase production. Frequencies of conjugal transfer were similar into diverse recipients (other gonococci, Neisseria flava, and Escherichia coli), which suggests that gonococci may transfer the plasmid promiscuously in nature.

The Global Programme to Eliminate Lymphatic Filariasis: health impact during its first 8 years (2000-2007).

During its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis provided more than 1900 million treatments with antifilarial drugs (albendazole, ivermectin and diethylcarbamazine) to at least 570 million people in 48 countries with endemic lymphatic filariasis (LF). As a result of this impressive global effort and an unprecedented public-private partnership, 8 years of mass drug administration (MDA) have prevented the spread of filarial infection to an estimated 6.6 million newborns, stopped the progression to clinical morbidity in 9.5 million individuals already infected with the parasites that cause LF, and drastically reduced the burden of several co-infections. The resulting health benefits of the MDA, in terms of reduced morbidity and disability-adjusted life-years, are thus enormous. The next step should be an analysis of the Global Programme's economic impact from its first 8 years of MDA.

Docking-based inverse virtual screening strategy for identification of novel protein targets for triclosan.

Triclosan (TCS) is chemically designated as 5-chloro-2-(2,4-dichlorophenoxy) phenol and is considered as endocrine-disrupting chemical (EDC). The various diseases found due to exposure of TCS, have been linked with modulation of the human enoyl-acyl carrier protein-reductase (hER). However, the new protein targets for TCS other than hER, which are responsible for various diseases, are still unknown. In the present study, a bioinformatics approach was used to identify new possible targets for TCS. A text mining study was initially performed to understand the association of TCS in various biochemical processes. Discovery studio software 4.1 was used to carry out inverse virtual screening for 226 numbers of pathway proteins by docking study using CHARMm based docking tool, and twenty proteins were screened. CDOCKER energy values lower than -12.65 kcal/mol was considered for the screening of selected proteins. Three new proteins; Receptor-interacting protein 1 (RIP1), Apoptosis signal-regulating kinase 1 (ASK1) and B-cell lymphoma 2 (Bcl-2) from Apoptosis Signaling Pathway revealed best CDOCKER energy with triclosan which was -26.88, -23.34 and -22.96 kcal/mol respectively. The interaction of TCS with RIP1 and ASK1 were mostly hydrophobic; however, hydrogen bond type interaction was found in TCS/Bcl2 complex. Therefore, docking-based inverse virtual screening study suggests that TCS has other targets rather than hER, which can modulate various biochemical processes. The docking protocol was validated through evaluation of root-mean-square deviation (RMSD), key interaction score system (KISS) and the relationship between the docking energy and toxicity data available in ToxCast database. Low RMSD value (0.55 ˚A) and high KISS score (0.66) along with higher correlation (R2 = 0.9798) between docking affinity and toxicity indicated that docking protocol can be used to optimize the binding energetics.