The effect of fear and situational motivation on online information avoidance: The case of COVID-19.

During the COVID-19 pandemic, a plethora of online sources for information and news dissemination have emerged. Extant research suggests that very quickly, individuals become disinterested and begin avoiding the information. In this study, we investigate how an individual's fear and situational motivation impact Online Information Avoidance. Using the self-determination theory and information avoidance theories, we argue that fear and external regulation are associated with increased Online Information Avoidance. We also argue that intrinsic motivation and identified regulation are associated with a decrease in Online Information Avoidance. Our findings suggest that fear, intrinsic motivation, and external regulation drive Online Information Avoidance, where intrinsic motivation is the most significant driver. We also found that identified regulation is a crucial inhibitor of Online Information Avoidance. While focusing on COVID-19, our study contributes to the broader information systems research literature and specifically to the information avoidance literature during a pandemic or a prolonged crisis. Our study's findings will be useful for governments, health organizations, and communities that utilize online platforms, forums, and related outlets to reach larger audiences for disseminating pertinent information and recommendations during a crisis.

Partnerships in the introduction of new routine vaccines in Bangladesh: evidence from a prospective process evaluation.

OBJECTIVE: To assess the contribution of partners in the introduction of two new vaccines concurrently: pneumococcal 10-valent conjugate vaccine (PCV-10) and inactivated polio vaccine (IPV) into the routine Expanded Programme on Immunization (EPI) in Bangladesh. DESIGN: We conducted a prospective process evaluation that included the theory of change development, root cause analysis and in-depth investigation. As part of process tracking, we reviewed relevant documents, observed trainers' and vaccinators' training and key stakeholder meetings. We analysed the data thematically. SETTING: We purposively selected eight Upazila (subdistrict) and one city corporation covering nine districts and seven administrative divisions of Bangladesh. PARTICIPANTS: Nineteen national key informants were interviewed and 16 frontline health workers were invited to the group discussions considering their involvement in the vaccine introduction process. RESULTS: The EPI experienced several challenges during the joint introduction of PCV-10 and IPV, such as frequent changes in the vaccine introduction schedule, delays in budget allocation, vaccine supply shortage and higher wastage rates of IPV. EPI addressed these challenges in collaboration with its partners, that is, the World Health Organization (WHO) and United Nations Children's Fund (UNICEF), who provided technical assistance to develop a training curriculum and communication materials and enhanced demand generation at the community level. In addition, the WHO conducted a country readiness assessment for PCV-10, and UNICEF supported vaccine shipment. Other government ministries, City Corporations and municipalities also supported the EPI. CONCLUSIONS: The partnership among the EPI stakeholders effectively addressed various operational challenges during the joint introduction of PCV-10 and IPV helped strengthen Bangladesh's immunisation systems. These accomplishments are attributed to several factors that should be supported and strengthened for future vaccine introductions in Bangladesh and other low and-middle countries.

The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1.

Binding of HIV-1 capsid (CA) to cleavage and polyadenylation specificity factor 6 (CPSF6) is hypothesized to provide a significant fitness advantage to in vivo viral replication, explaining why CA-CPSF6 interactions are strictly conserved in primate lentiviruses. We recently identified a Q4R mutation in CA after propagation of an interferon (IFN)-ß-hypersensitive CA mutant, RGDA/Q112D (H87R, A88G, P90D, P93A and Q112D) virus, in IFN-ß-treated cells. The Q4R substitution conferred significant IFN-ß resistance to the RGDA/Q112D virus by affecting several properties of the virus, including the sensitivity to myxovirus resistance protein B (MxB), the kinetics of reverse transcription, and the initiation of uncoating. Notably, the Q4R substitution restored the CPSF6 interaction of the RGDA/Q112D virus. To better understand how the Q4R substitution modulated the CA-CPSF6 interaction, we generated a series of CA mutants harboring substitutions at the 4th and 112th residues. In contrast to the effect in the RGDA/Q112D background, the Q4R substitution diminished CA-CPSF6 interaction in an otherwise wild-type virus. Our genetic and structural analyses revealed that while either the Q4R or Q112D substitution impaired CA-CPSF6 interaction, the combination of these substitutions restored this interaction. These results suggest that the 4th and 112th residues in HIV-1 CA cooperatively modulate CA-CPSF6 interactions, further highlighting the tremendous levels of plasticity in primate lentivirus CA, which is one of the barriers to antiretroviral therapy in HIV-1-infected individuals.

Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid.

Type I interferons (IFNs), including alpha IFN (IFN-α) and IFN-ß, potently suppress HIV-1 replication by upregulating IFN-stimulated genes (ISGs). The viral capsid protein (CA) partly determines the sensitivity of HIV-1 to IFNs. However, it remains to be determined whether CA-related functions, including utilization of known host factors, reverse transcription, and uncoating, affect the sensitivity of HIV-1 to IFN-mediated restriction. Recently, we identified an HIV-1 CA variant that is unusually sensitive to IFNs. This variant, called the RGDA/Q112D virus, contains multiple mutations in CA: H87R, A88G, P90D, P93A, and Q112D. To investigate how an IFN-hypersensitive virus can evolve to overcome IFN-ß-mediated blocks targeting the viral capsid, we adapted the RGDA/Q112D virus in IFN-ß-treated cells. We successfully isolated IFN-ß-resistant viruses which contained either a single Q4R substitution or the double amino acid change G94D/G116R. These two IFN-ß resistance mutations variably changed the sensitivity of CA binding to human myxovirus resistance B (MxB), cleavage and polyadenylation specificity factor 6 (CPSF6), and cyclophilin A (CypA), indicating that the observed loss of sensitivity was not due to interactions with these known host CA-interacting factors. In contrast, the two mutations apparently functioned through distinct mechanisms. The Q4R mutation dramatically accelerated the kinetics of reverse transcription and initiation of uncoating of the RGDA/Q112D virus in the presence or absence of IFN-ß, whereas the G94D/G116R mutations affected reverse transcription only in the presence of IFN-ß, most consistent with a mechanism of the disruption of binding to an unknown IFN-ß-regulated host factor. These results suggest that HIV-1 can exploit multiple, known host factor-independent pathways to avoid IFN-ß-mediated restriction by altering capsid sequences and subsequent biological properties.IMPORTANCE HIV-1 infection causes robust innate immune activation in virus-infected patients. This immune activation is characterized by elevated levels of type I interferons (IFNs), which can block HIV-1 replication. Recent studies suggest that the viral capsid protein (CA) is a determinant for the sensitivity of HIV-1 to IFN-mediated restriction. Specifically, it was reported that the loss of CA interactions with CPSF6 or CypA leads to higher IFN sensitivity. However, the molecular mechanism of CA adaptation to IFN sensitivity is largely unknown. Here, we experimentally evolved an IFN-ß-hypersensitive CA mutant which showed decreased binding to CPSF6 and CypA in IFN-ß-treated cells. The CA mutations that emerged from this adaptation indeed conferred IFN-ß resistance. Our genetic assays suggest a limited contribution of known host factors to IFN-ß resistance. Strikingly, one of these mutations accelerated the kinetics of reverse transcription and uncoating. Our findings suggest that HIV-1 selected multiple, known host factor-independent pathways to avoid IFN-ß-mediated restriction.

Implementation of the World's largest measles-rubella mass vaccination campaign in Bangladesh: a process evaluation.

BACKGROUND: Gavi, the Vaccine Alliance, supported a mass vaccination Measles-Rubella Campaign (MRC) in Bangladesh during January-February 2014. METHODS: We conducted a mixed-method process evaluation to understand the successes and challenges in implementation of the MRC. We reviewed documents for the MRC and the immunization programme in Bangladesh; observed meetings, vaccination sessions, and health facilities; and conducted 58 key informant interviews, 574 exit interviews with caregivers and 156 brief surveys with stakeholders involved in immunization. Our theory of Change for vaccination delivery guided our assessment of ideal implementation milestones and indicators to compare with the actual implementation processes. RESULTS: We identified challenges relating to country-wide political unrest, administrative and budgetary delays, shortage of transportation, problems in registration of target populations, and fears about safety of the vaccine. Despite these issues, a number of elements contributed to the successful launch of the MRC. These included: the comprehensive design of the campaign; strong partnerships between immunization authorities in the government system, Alliance partners, and civil society actors; and motivated and skilled health workers at different levels of the health system. CONCLUSIONS: The successful implementation of the MRC in spite of numerous contextual and operational challenges demonstrated the adaptive capacity of the national immunization programme and its partners that has positive implications for future introductions of Gavi-supported vaccines.

Naturally Occurring Mutations in HIV-1 CRF01_AE Capsid Affect Viral Sensitivity to Restriction Factors.

TRIM5α and MxB are known as restriction factors that inhibit the early step of intracellular HIV-1 replication cycle. Both factors are believed to interact with the incoming virus core to suppress HIV-1 infection. The extreme diversity of HIV-1 is thought to be a consequence of its propensity to mutate to escape immune responses and host restriction factors. We recently determined the capsid sequences for 144 HIV-1 CRF01_AE viruses obtained in Thailand from 2005 to 2011. In this study, we further analyzed the amino acid variations among the capsid sequences of 204 HIV-1 CRF01_AE obtained in Thailand and China, including 84 of the aforementioned 144 viruses, to detect mutations permitting escape from restriction by host factors. We found a characteristic combination of E79D, V83T, and H87Q in sequences from Chinese viruses and subsequently showed that this combination conferred partial resistance to MxB. Interestingly, this combination conferred resistance to human TRIM5α as well. The H87Q mutation alone conferred resistance to MxB in the CRF01_AE background, but not in subtype B virus. In contrast, the H87Q mutation alone conferred resistance to human TRIM5α in both the CFR01_AE and subtype B backgrounds. BLAST analysis revealed the presence of the E79D, V83T, and H87Q combination in CRF01_AE viruses isolated not only in China but also in many other countries. Although the mechanistic details as well as precise role of MxB antiviral activity in infected individuals remain to be clarified, our data suggest an interaction between MxB and the HIV-1 capsid in vivo.

Mild Respiratory Illness Among Young Children Caused by Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in Dhaka, Bangladesh, 2011.

Background: In March 2011, a multidisciplinary team investigated 2 human cases of highly pathogenic avian influenza A(H5N1) virus infection, detected through population-based active surveillance for influenza in Bangladesh, to assess transmission and contain further spread. Methods: We collected clinical and exposure history of the case patients and monitored persons coming within 1 m of a case patient during their infectious period. Nasopharyngeal wash specimens from case patients and contacts were tested with real-time reverse-transcription polymerase chain reaction, and virus culture and isolates were characterized. Serum samples were tested with microneutralization and hemagglutination inhibition assays. We tested poultry, wild bird, and environmental samples from case patient households and surrounding areas for influenza viruses. Results: Two previously healthy case patients, aged 13 and 31 months, had influenzalike illness and fully recovered. They had contact with poultry 7 and 10 days before illness onset, respectively. None of their 57 contacts were subsequently ill. Clade 2.2.2.1 highly pathogenic avian influenza H5N1 viruses were isolated from the case patients and from chicken fecal samples collected at the live bird markets near the patients' dwellings. Conclusion: Identification of H5N1 cases through population-based surveillance suggests possible additional undetected cases throughout Bangladesh and highlights the importance of surveillance for mild respiratory illness among populations frequently exposed to infected poultry.

A comparison of pregnancy outcomes using two diagnostic criteria for gestational diabetes mellitus-carpenter coustan criteria and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#To compare the maternal and perinatal outcomes in women with GDM diagnosed by Carpenter & Coustan (CC) criteria and by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. @*Methodology@#A cross-sectional comparative study was conducted using data of women who were screened and diagnosed with GDM between April 2006-March 2007 using the CC criteria and April 2013-March 2014 using IADPSG criteria. Maternal and perinatal outcomes were noted. Means and proportions were calculated for continuous and categorical variables respectively. Data were analyzed using t-test for normally distributed data and Mann-Whitney U test for those that were not normally distributed. Pearson Chi-square test was used to find an association between the various outcomes between the two groups.@*Results@#Among 500 pregnant women screened, 36 were diagnosed GDM in the CC group. In the IADPSG group, 733 women were screened and 167 were diagnosed GDM. Prevalence of GDM was 7.2% in CC group and 22.78% in IADPSG group (p=0.000). There was a statistically significant difference in the number of women who developed hypertension and polyhydramnios among the two groups. Women who had an operative vaginal delivery (16.67% vs. 6.6%, p=0.085) and mean birth weight (3.10±0.55 kg vs. 2.97±0.48 kg, p=0.165) were higher in CC group than the IADPSG group. Among the perinatal outcomes, a statistically significant improvement was found in the number of neonates developing respiratory distress syndrome (p=0.000) and hyperbilirubinemia (p=0.000), when the IADPSG criteria were used. @*Conclusion@#There is a statistically significant difference between the maternal and neonatal outcomes when the newer IADPSG criteria were used for diagnosis of GDM.

Novel mutant human immunodeficiency virus type 1 strains with high degree of resistance to cynomolgus macaque TRIMCyp generated by random mutagenesis.

Old World monkey TRIM5α strongly suppresses human immunodeficiency virus type 1 (HIV-1) replication. A fusion protein comprising cynomolgus macaque (CM) TRIM5 and cyclophilin A (CM TRIMCyp) also potently suppresses HIV-1 replication. However, CM TRIMCyp fails to suppress a mutant HIV-1 that encodes a mutant capsid protein containing a SIVmac239-derived loop between α-helices 4 and 5 (L4/5). There are seven amino acid differences between L4/5 of HIV-1 and SIVmac239. Here, we investigated the minimum numbers of amino acid substitutions that would allow HIV-1 to evade CM TRIMCyp-mediated suppression. We performed random PCR mutagenesis to construct a library of HIV-1 variants containing mutations in L4/5, and then we recovered replication-competent viruses from CD4+ MT4 cells that expressed high levels of CM TRIMCyp. CM TRIMCyp-resistant viruses were obtained after three rounds of selection in MT4 cells expressing CM TRIMCyp and these were found to contain four amino acid substitutions (H87R, A88G, P90D and P93A) in L4/5. We then confirmed that these substitutions were sufficient to confer CM TRIMCyp resistance to HIV-1. In a separate experiment using a similar method, we obtained novel CM TRIM5α-resistant HIV-1 strains after six rounds of selection and rescue. Analysis of these mutants revealed that V86A and G116E mutations in the capsid region conferred partial resistance to CM TRIM5α without substantial fitness cost when propagated in MT4 cells expressing CM TRIM5α. These results confirmed and further extended the previous notion that CM TRIMCyp and CM TRIM5α recognize the HIV-1 capsid in different manners.

A comparison of pregnancy outcomes using two diagnostic criteria for Gestational Diabetes Mellitus-Carpenter Coustan Criteria and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#To compare the maternal and perinatal outcomes in women with GDM diagnosed by Carpenter & Coustan (CC) criteria and by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. @*Methodology@#A cross-sectional comparative study was conducted using data of women who were screened and diagnosed with GDM between April 2006-March 2007 using the CC criteria and April 2013-March 2014 using IADPSG criteria. Maternal and perinatal outcomes were noted. Means and proportions were calculated for continuous and categorical variables respectively. Data were analyzed using t-test for normally distributed data and Mann-Whitney U test for those that were not normally distributed. Pearson Chi-square test was used to find an association between the various outcomes between the two groups. @*Results@#Among 500 pregnant women screened, 36 were diagnosed GDM in the CC group. In the IADPSG group, 733 women were screened and 167 were diagnosed GDM. Prevalence of GDM was 7.2% in CC group and 22.78% in IADPSG group (p=0.000). There was a statistically significant difference in the number of women who developed hypertension and polyhydramnios among the two groups. Women who had an operative vaginal delivery (16.67% vs. 6.6%, p=0.085) and mean birth weight (3.10±0.55 kg vs. 2.97±0.48 kg, p=0.165) were higher in CC group than the IADPSG group. Among the perinatal outcomes, a statistically significant improvement was found in the number of neonates developing respiratory distress syndrome (p=0.000) and hyperbilirubinemia (p=0.000), when the IADPSG criteria were used. @*Conclusion@#There is a statistically significant difference between the maternal and neonatal outcomes when the newer IADPSG criteria were used for diagnosis of GDM.

Non-Markovian properties and multiscale hidden Markovian network buried in single molecule time series.

We present a novel scheme to extract a multiscale state space network (SSN) from single-molecule time series. The multiscale SSN is a type of hidden Markov model that takes into account both multiple states buried in the measurement and memory effects in the process of the observable whenever they exist. Most biological systems function in a nonstationary manner across multiple timescales. Combined with a recently established nonlinear time series analysis based on information theory, a simple scheme is proposed to deal with the properties of multiscale and nonstationarity for a discrete time series. We derived an explicit analytical expression of the autocorrelation function in terms of the SSN. To demonstrate the potential of our scheme, we investigated single-molecule time series of dissociation and association kinetics between epidermal growth factor receptor (EGFR) on the plasma membrane and its adaptor protein Ash/Grb2 (Grb2) in an in vitro reconstituted system. We found that our formula successfully reproduces their autocorrelation function for a wide range of timescales (up to 3 s), and the underlying SSNs change their topographical structure as a function of the timescale; while the corresponding SSN is simple at the short timescale (0.033-0.1 s), the SSN at the longer timescales (0.1 s to ~3 s) becomes rather complex in order to capture multiscale nonstationary kinetics emerging at longer timescales. It is also found that visiting the unbound form of the EGFR-Grb2 system approximately resets all information of history or memory of the process.