Genetics of immune response to Epstein-Barr virus: prospects for multiple sclerosis pathogenesis.

Epstein-Barr virus (EBV) infection has been advocated as a prerequisite for developing multiple sclerosis (MS) and possibly the propagation of the disease. However, the precise mechanisms for such influences are still unclear. A large-scale study investigating the host genetics of EBV serology and related clinical manifestations, such as infectious mononucleosis (IM), may help us better understand the role of EBV in MS pathogenesis. This study evaluates the host genetic factors that influence serological response against EBV and history of IM and cross-evaluates them with MS risk and genetic susceptibility in the Swedish population. Plasma IgG antibody levels against EBV nuclear antigen-1 (EBNA-1, truncated=aa[325-641], peptide=aa[385-420]) and viral capsid antigen p18 (VCAp18) were measured using bead-based multiplex serology for 8744 MS cases and 7229 population-matched controls. The MS risk association for high/low EBV antibody levels and history of IM was compared to relevant clinical measures along with sex, age at sampling, and associated HLA allele variants. Genome-wide and HLA allele association analyses were also performed to identify genetic risk factors for EBV antibody response and IM history. Higher antibody levels against VCAp18 (OR=1.74, 95% CI=1.60-1.88) and EBNA-1, particularly the peptide (OR=3.13, 95% CI=2.93-3.35), were associated with an increased risk for MS. The risk increased with higher anti-EBNA-1 IgG levels up to twelve times the reference risk. We also identified several independent HLA haplotypes associated with EBV serology overlapping with known MS risk alleles (e.g., DRB1*15:01). Although there were several candidates, no variants outside the HLA region reached genome-wide significance. Cumulative HLA risk for anti-EBNA-1 IgG levels, particularly the peptide fragment, was strongly associated with MS. In contrast, the genetic risk for high anti-VCAp18 IgG levels was not as strongly associated with MS risk. IM history was not associated with class II HLA genes but negatively associated with A*02:01, which is protective against MS. Our findings emphasize that the risk association between anti-EBNA-1 IgG levels and MS may be partly due to overlapping HLA associations. Additionally, the increasing MS risk with increasing anti-EBNA-1 levels would be consistent with a pathogenic role of the EBNA-1 immune response, perhaps through molecular mimicry. Given that high anti-EBNA-1 antibodies may reflect a poorly controlled T-cell defense against the virus, our findings would be consistent with DRB1*15:01 being a poor class II antigen in the immune defense against EBV. Lastly, the difference in genetic control of IM supports the independent roles of EBNA-1 and IM in MS susceptibility.

Head trauma results in manyfold increased risk of multiple sclerosis in genetically susceptible individuals.

BACKGROUND: Large register-based studies have reported an association between head trauma and increased risk of multiple sclerosis (MS). We aimed to investigate possible interactions between head trauma and MS-associated HLA genes in relation to MS risk. METHODS: We used a Swedish population-based case-control study (2807 incident cases, 5950 matched controls with HLA genotypes available for 2057 cases, 2887 controls). Subjects with and without a history of self-reported head trauma were compared regarding MS risk, by calculating ORs with 95% CIs using logistic regression models. Additive interaction between head trauma, HLA-DRB1*1501 and absence of HLA-A*0201, was assessed by calculating the attributable proportion (AP) due to interaction. RESULTS: A history of head trauma was associated with a 30% increased risk of subsequently developing MS (OR 1.34, 95% CI 1.17 to 1.53), with a trend showing increased risk of MS with increasing number of head impacts (p=0.03). We observed synergistic effects between recent head trauma and HLA-DRB1*15:01 as well as absence of HLA*02:01 in relation to MS risk (each AP 0.40, 95% CI 0.1 to 0.7). Recent head trauma in individuals with both genetic risk factors rendered an 18-fold increased risk of MS, compared with those with neither the genetic risk factors nor a history of head trauma (OR 17.7, 95% CI 7.13 to 44.1). CONCLUSIONS: Our findings align with previous observations of a dose-dependent association between head trauma and increased risk of MS and add a novel aspect of this association by revealing synergistic effects between recent head trauma and MS-associated HLA genes.

Association between sun exposure habits and disease progression in multiple sclerosis.

BACKGROUND AND PURPOSE: Higher latitude has been associated with increased occurrence of multiple sclerosis (MS) and with more severe disease. The aim was to study the impact of sun exposure habits on MS disease progression and health-related quality of life. METHODS: Patients from a population-based case-control study were categorized based on sun exposure habits at diagnosis and were followed up to 15 years post-diagnosis through the Swedish MS registry (n = 3314) with regard to changes in Expanded Disability Status Scale (EDSS). Linear mixed models were used to analyse long-term changes, while Cox regression models, with 95% confidence intervals, were used to investigate outcomes, including 24-week confirmed diasability worsening, EDSS3, EDSS4, and physical worsening as measured by the physical component of the Multiple Sclerosis Impact Scale 29. RESULTS: Compared to average sun exposure (median value), low exposure to sunlight was associated with faster EDSS progression, increased risk of confirmed disability worsening (hazard ratio [HR] 1.48, 95% CI 1.21-1.81), increased risk of reaching EDSS 3 (HR 1.35, 95% CI 1.02-1.79), EDSS 4 (HR 1.47, 95% CI 1.01-2.20) and self-reported physical worsening (HR 1.27, 95% CI 1.00-1.62). Significant trends revealed a lower risk of unfavourable outcomes with increasing sun exposure. CONCLUSIONS: Very low levels of sun exposure are associated with worse disease progression and health-related quality of life in patients with MS.

Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study.

BACKGROUND: Shift work, which often results in sleep deprivation and circadian desynchrony, has been associated with increased risk of multiple sclerosis (MS). We aimed at studying the impact of sleep duration, circadian disruption and sleep quality on MS risk. METHODS: We used a Swedish population-based case-control study (2075 cases, 3164 controls). Aspects of sleep were associated with MS risk by calculating OR with 95% CIs using logistic regression models. RESULTS: Compared with sleeping 7-9 hours/night during adolescence, short sleep (<7 hours/night) was associated with increased risk of developing MS (OR 1.4, 95% OR 1.1-1.7). Similarly, subjective low sleep quality during adolescence increased the risk of subsequently developing MS (OR 1.5, 95% CI 1.3 to 1.9), whereas phase shift did not significantly influence the risk. Our findings remained similar when those who worked shifts were excluded. CONCLUSIONS: Insufficient sleep and low sleep quality during adolescence seem to increase the risk of subsequently developing MS. Sufficient restorative sleep at young age, needed for adequate immune functioning, may be a preventive factor against MS.

Influence of oral tobacco versus smoking on multiple sclerosis disease activity and progression.

We aimed to study the influence of smoking habits, exposure to passive smoking and snuff use on disease progression, cognitive performance and quality of life in patients with multiple sclerosis (MS). METHOD: Patients from two population-based case-control studies were categorised based on tobacco exposure at diagnosis and were followed up to 15 years post diagnosis through the Swedish MS registry (n=9089) regarding changes in Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale 29 and Symbol Digit Modalities Test. We used linear mixed models to analyse long-term changes, and Cox regression models with 95% CI using 24-week confirmed disability worsening, reaching EDSS 3 and EDSS 4, respectively, physical and psychological worsening and cognitive disability worsening as end points. The influence of smoking cessation post diagnosis was also investigated. RESULTS: Compared with non-smokers, current smokers had a faster EDSS progression (ßcurrent smoking×time=0.03, 95% CI 0.02 to 0.04). A faster EDSS progression was also associated with passive smoking (ßcurrent passive smoking×time=0.04, 95% CI 0.03 to 0.06). Smoke exposure negatively impacted all secondary outcomes. Those who continued smoking had worse outcomes than those who stopped smoking post diagnosis. Snuff users had a more favourable EDSS progression, compared with never users. CONCLUSIONS: Our findings indicate that both smoking and passive smoking have a negative influence on MS and that smoking cessation post diagnosis may be an important secondary preventive measure. Snuff use was associated with slower disease progression, suggesting that nicotine replacement therapy could be an attractive way to increase the chance of quitting smoking among patients with MS.

Inverse association between Mediterranean diet and risk of multiple sclerosis.

OBJECTIVE: There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple sclerosis (MS). METHODS: We used a population-based case-control study recruiting incident cases of MS (1953 cases, 3557 controls). Subjects with different dietary habits 5 years prior to MS diagnosis were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Adjustment was made for a large number of environmental and lifestyle habits, including ancestry, smoking, alcohol consumption, body mass index, physical activity, and sun exposure habits. RESULTS: Mediterranean diet was associated with lower risk of developing MS (adjusted OR = 0.54, 95% CI: 0.34-0.86, p = 0.009), compared with Western-style diet. There was no significant association between vegetarian/vegan diet and MS risk (adjusted OR = 0.96, 95% CI: 0.75-1.24, p = 0.976), nor between diet with low glycemic index and MS risk (adjusted OR = 0.93, 95% CI: 0.60-1.42, p = 0.518). CONCLUSIONS: Mediterranean diet may exert a protective influence regarding the risk of subsequently developing MS compared with Western-style diet.

Observed associations between indicators of socioeconomic status and risk of multiple sclerosis in Sweden are explained by a few lifestyle-related factors.

BACKGROUND AND PURPOSE: The association between socioeconomic status (SES) and the risk of multiple sclerosis (MS) is unclear. The aim was to study whether a potential association between indicators of SES and MS risk in Sweden is explained by lifestyle/environmental factors. METHODS: Using the Swedish MS registry and the Swedish patient registries, a register study was performed comprising all cases diagnosed with MS in Sweden between 1990 and 2018 (N = 24,729) and five randomly selected controls per case, matched by year and age at disease onset, sex and residential area at disease onset. Data from two matched case-control studies combined comprising data on environment/lifestyle factors (7193 cases, 9609 controls, inclusion period 2005-2018) were also utilized. For all participants, information regarding ancestry, formal education (available 1990-2018) and family income (available 1998-2018) was retrieved from the National Board of Health and Welfare. RESULTS: The registry study revealed no association between education and MS risk, whereas an income exceeding the upper quartile was associated with lower MS risk compared to having an income in the lowest quartile (odds ratio 0.86, 95% confidence interval 0.82-0.90). These findings were replicated in the crude analyses of the case-control study. However, after adjustment for confounding, no association was observed between income and risk of MS. CONCLUSIONS: Education and income were not associated with occurrence of MS after adjustment for a few lifestyle-related factors (smoking, alcohol consumption, body mass index and sun exposure habits), indicating that SES has no influence on MS risk besides its association with these lifestyle factors in the Swedish context.

Prevalence and pattern of retinopathy of prematurity at two national referral hospitals in Uganda: a cross-sectional study.

BACKGROUND: Retinopathy of prematurity (ROP) is a leading cause of blindness in children and an ROP epidemic is predicted this decade in sub-Saharan Africa. With the increasing survival rate of preterm babies in Uganda, and no data on ROP prevalence, there is a need to assess the burden of ROP to inform preventive strategies and targeted screening. METHODS: We conducted a two-center cross-sectional study of preterm (< 37 weeks gestational age) infants from the neonatal units of Kawempe National Referral Hospital (KNRH) and Mulago Specialised Women and Neonatal Hospital (MSWNH) from August 2022 to October 2022. An ophthalmologist examined all participants using an indirect ophthalmoscope with a + 20D convex lens and captured digital images using a Volk iNview™ Fundus Camera. The collected data were entered into Epidata 4.2 and exported to Stata 14.0 for analysis. RESULTS: 331 preterm infants enrolled in this study. The oxygen received was unblended. The mean gestational age was 30.4 ± 2.7 weeks, and the mean birth weight was 1597 ± 509 g. 18/101 (17.8%) were found to have any ROP amongst the preterm infants recruited from MSWNH, 1/230 (0.4%) from KNRH [95% CI] had any stage of ROP (i.e. stage 5). Of these, 8 (42.1%) had stage 2 ROP. Infants with a birth weight below 1500 g were 10 times more likely to have ROP than those among infants with a birth weight more than 1500 g [AOR: 10.07 (2.71-37.44)]. Infants who were not fed exclusively on breast milk had higher odds of having ROP than those exclusively fed on breast milk [AOR: 7.82(1.92-31.82)]. CONCLUSION: 6% of preterm infants born in two tertiary hospitals in Uganda were found to have ROP. Lack of exclusive feeding on breast milk and birth weight of less than 1500 g were strong predictors of ROP. The higher prevalence of ROP in MSWNH calls for cautious use of oxygen among preterms. We recommend targeted ROP screening for those at risk.

High antibody levels against human herpesvirus-6A interact with lifestyle factors in multiple sclerosis development.

BACKGROUND: Infection with human herpesvirus 6A (HHV-6A) has been suggested to increase multiple sclerosis (MS) risk. However, potential interactions between HHV-6A and environmental/lifestyle risk factors for MS have not previously been studied. METHODS: We used two Swedish population-based case-control studies comprising 5993 cases and 5995 controls. Using logistic regression models, subjects with different HHV-6A antibody levels, environmental exposures, and lifestyle habits were compared regarding MS risk, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Potential interactions between high HHV-6A antibody levels and common environmental exposures and lifestyle factors were evaluated on the additive scale. RESULTS: High HHV-6A antibody levels were associated with increased risk of developing MS (OR = 1.5, 95% CI = 1.4-1.6). Regarding MS risk, significant interactions were observed between high HHV-6A antibody levels and both smoking (attributable proportion (AP) = 0.2, 95% CI = 0.1-0.3), low ultraviolet radiation (UVR) exposure (AP = 0.3, 95% CI = 0.1-0.4), and low vitamin D levels (AP = 0.3, 95% CI = 0.0-0.6). CONCLUSION: High HHV-6A antibody levels are associated with increased MS risk and act synergistically with common environmental/lifestyle risk factors for MS. Further research is needed to investigate potential mechanisms underlying the interactions presented in this study.

Factors affecting the risk of relapsing-onset and progressive-onset multiple sclerosis.

OBJECTIVE: It has been debated whether the different clinical disease courses in multiple sclerosis (MS) are the consequence of different pathogenic mechanisms, with distinct risk factors, or if all MS clinical phenotypes are variations of similar underlying disease mechanisms. We aimed to study environmental risk factors and their interactions with human leucocyte antigen DRB1*15:01 with regards to relapsing-onset and progressive-onset MS. METHODS: We used two Swedish population-based case-control studies, including 7520 relapsing-onset cases, 540 progressive-onset cases and 11 386 controls matched by age, sex and residential area. Logistic regression was used to estimate ORs with 95% CIs for associations between the different MS phenotypes and a number of environmental and lifestyle factors. Interaction between the DRB1*15:01 allele and environmental risk factors was evaluated on the additive scale. RESULTS: All environmental and lifestyle factors associated with risk of developing MS apply to both relapsing-onset and progressive-onset disease. Smoking, obesity and Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibody levels were associated with increased risk of both MS phenotypes, whereas snuff use, alcohol consumption and sun exposure were associated with reduced risk. Additive interactions between DRB1*15:01 and smoking, obesity, EBNA-1 antibody levels and sun exposure, respectively, occurred to increase MS risk regardless of the clinical phenotype. INTERPRETATION: Our finding that the same environmental and lifestyle factors affect both relapsing-onset and progressive-onset MS supports the notion that the different clinical phenotypes share common underlying disease mechanisms.

DRB1-environment interactions in multiple sclerosis etiology: results from two Swedish case-control studies.

OBJECTIVE: We aimed to investigate the influence of environmental risk factors for multiple sclerosis (MS) in different genetic contexts, and study if interactions between environmental factors and human leucocyte antigen (HLA) genes differ in magnitude according to heterozygocity and homozygocity for HLA-DRB1*15:01. METHODS: Using population-based case-control studies (6985 cases, 6569 controls), subjects with different genotypes and smoking, EBNA-1 status and adolescent Body Mass status, were compared regarding MS risk, by calculating OR with 95% CI employing logistic regression. The interaction between different genotypes and each environmental factor was evaluated on the additive scale. RESULTS: The effect of each DRB1*15:01 allele on MS risk was additive on the log-odds scale for each additional allele. Interaction between DRB1*15:01 and each assessed environmental factor was of similar magnitude regardless of the number of DRB1*15:01 alleles, although ORs were affected. When any of the environmental factors were present in DRB1*15:01 carriers without the protective A*02:01 allele, a three-way interaction occurred and rendered high ORs, especially among DRB1*15:01 homozygotes (OR 20.0, 95% CI 13.1 to 30.5 among smokers, OR 21.9, 95% CI 15.0 to 31.8 among those with elevated EBNA-1 antibody levels, and OR 44.3, 95% CI 13.5 to 145 among those who reported adolescent overweight/obesity). CONCLUSIONS: The strikingly increased MS risk among DRB*15:01 homozygotes exposed to any of the environmental factors is a further argument in favour of these factors acting on immune-related mechanisms. The data further reinforce the importance of preventive measures, in particular for those with a genetic susceptibility to MS.

Cotinine as a measure of smoking in observational studies of multiple sclerosis.

Studies using cotinine levels to define smokers have generally failed to detect an association between smoking and multiple sclerosis (MS). Using a Swedish population-based case-control study, we show that associations in relation to MS risk and progression differ considerably depending on how smoking is measured. The risk of conversion into secondary progressive disease was increased among smokers when self-reported smoking history, but not presumed cotinine levels, was used to define smokers. Defining smoking by cotinine levels without distinguishing between different sources of nicotine may lead to severely biased estimates of the association between smoking and both MS risk and progression.

Low sun exposure acts synergistically with high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels in multiple sclerosis etiology.

BACKGROUND: Among multiple sclerosis (MS) patients, an association has been observed between low levels of vitamin D and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels. However, whether sun exposure/vitamin D moderates the role of Epstein-Barr virus (EBV) infection in MS etiology is unclear. We aimed to investigate potential synergistic effects between low sun exposure and elevated EBNA-1 antibody levels regarding MS risk. METHODS: We used a population-based case-control study involving 2017 incident cases of MS and 2443 matched controls. We used logistic regression models to calculate the odds ratios of MS with 95% confidence intervals (CIs) in subjects with different sun exposure habits and EBNA-1 status. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). RESULTS: Low sun exposure acted synergistically with high EBNA-1 antibody levels (AP 0.2, 95% CI 0.03-0.3) in its association to increased MS risk. The interaction was present regardless of HLA-DRB1*15:01 status. CONCLUSIONS: Low sun exposure may either directly, or indirectly by affecting vitamin D levels, synergistically reinforce pathogenic mechanisms, such as aspects of the adaptive immune response, related to MS risk conveyed by EBV infection.

Telehealth Training During the COVID-19 Pandemic: A Feasibility Study of Large Group Multiplatform Telesimulation Training.

Background:Video telehealth is an important tool for health care delivery during the COVID-19 pandemic. Given physical distancing recommendations, access to traditional in-person telehealth training for providers has been limited. Telesimulation is an alternative to in-person telehealth training. Telesimulation training with both remote participants and facilitators using telehealth software has not been described.Objective:We investigated the feasibility of a large group telesimulation provider training of telehealth software for remote team leadership skills with common neonatal cases and procedures.Methods:We conducted a 90-min telesimulation session with a combination of InTouch™ provider access software and Zoom™ teleconferencing software. Zoom facilitators activated InTouch software and devices and shared their screen with remote participants. Participants rotated through skill stations and case scenarios through Zoom and directed bedside facilitators to perform simulated tasks using the shared screen and audio connection. Participants engaged in a debrief and a pre- and postsurvey assessing participants' comfort and readiness to use telemedicine. Data were analyzed using descriptive statistics and paired t tests.Results:Twenty (n = 20) participants, five Zoom and eight bedside facilitators participated. Twenty-one (21) pre- and 16 postsurveys were completed. Most participants were attending neonatologists who rarely used telemedicine software. Postsession, participants reported increased comfort with some advanced InTouch features, including taking and sharing pictures with the patient (p < 0.01) and drawing on the shared image (p < 0.05), but less comfort with troubleshooting technical issues, including audio and stethoscope (p < 0.01). Frequently stated concerns were troubleshooting technical issues during a call (75%, n = 16) and personal discomfort with telemedicine applications and technology (56%, n = 16).Conclusion:Large group telesimulation is a feasible way to offer telehealth training for physicians and can increase provider comfort with telehealth software.

The influence of human leukocyte antigen-DRB1*15:01 and its interaction with smoking in MS development is dependent on DQA1*01:01 status.

BACKGROUND: HLA-DRB1*15:01, absence of HLA-A*02:01, and smoking interact to increase multiple sclerosis (MS) risk. OBJECTIVE: To analyze whether MS-associated human leukocyte antigen (HLA) alleles, apart from DRB1*15:01 and absence of A*02:01, interact with smoking in MS development, and to explore whether the established HLA-smoking interaction is affected by the DQA1*01:01 allele, which confers a protective effect only in the presence of DRB1*15:01. METHODS: In two Swedish population-based case-control studies (5838 cases, 5412 controls), subjects with different genotypes and smoking habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals employing logistic regression. Interaction on the additive scale between different genotypes and smoking was evaluated. RESULTS: The DRB1*08:01 allele interacted with smoking to increase MS risk. The interaction between DRB1*15:01 and both the absence of A*02:01 and smoking was confined to DQA1*01:01 negative subjects, whereas no interactions occurred among DQA1*01:01 positive subjects. CONCLUSION: Multifaceted interactions take place between different class II alleles and smoking in MS development. The influence of DRB1*15:01 and its interaction with the absence of A*02:01 and smoking is dependent on DQA1*01:01 status which may be due to differences in the responding T-cell repertoires.

Short- and long-term mortality following hypnotic use.

Potential long-term consequences of hypnotics remain controversial. We used the prospective Swedish National March Cohort, a study based on 41,695 participants with a mean follow-up duration of 18.9 years. Logistic regression models and Cox proportional hazards models with attained age as timescale were used to assess associations of hypnotic use with short- and long-term mortality. The proportion of subjects who initiated or discontinued hypnotic use during follow-up was substantial. All groups of hypnotics were associated with increased mortality within 2 years after a first prescription, with an overall OR of 2.38 (95% CI, 2.13-2.66). The association was more pronounced among subjects younger than 60 years (OR, 6.16; 95% CI, 3.98-9.52). There was no association between hypnotic use and long-term mortality. The association between hypnotic use and increased mortality was thus restricted to a relatively short period after treatment initiation, and may be explained in terms of confounding by indication.

Delayed initiation of enteral feeds is associated with postnatal growth failure among preterm infants managed at a rural hospital in Uganda.

BACKGROUND: Prematurity is the leading cause of mortality in children under 5 years of age globally and is also frequently associated with postnatal growth failure (PGF). Although most preterm births occur in low resource settings, little is known about their postnatal growth outcomes especially in rural areas. We evaluated the incidence and factors associated with PGF among preterm infants managed at a rural hospital in Uganda. METHODS: Retrospective cohort study of preterm infants discharged from Kiwoko Hospital neonatal intensive care unit (NICU) from July 2017 to June 2018. Inclusion criteria included gestational age 26 up to but not including 37 weeks, admission within 24 h of birth and at least 7 days hospital stay. Exclusion criteria included major congenital anomalies and missing gestational age or birth weight. Birth and discharge weights from clinical notes were plotted on Fenton 2013 growth charts. Gestation age was determined by last normal menstruation period (LNMP), extracted from the mother's antenatal card or early obstetric ultrasound scan reports. Postnatal growth failure was diagnosed if discharge weight was less than the 10th percentile for estimated gestational age. Other data from the clinical notes included demographic characteristics, neonatal morbidities as assigned by the attending physician and infant feeding practices. Multivariable logistic regression was used to explore factors associated with PGF. RESULTS: A total of 349 preterm infants with a mean gestational age of 31 (range 26 to 36) weeks were included. The incidence proportion of PGF was 254/349 (73%). Factors significantly associated with postnatal growth failure included: delayed initiation of enteral feeds [AOR = 3.70, 95% (CI 1.64 to 8.33)], sepsis [AOR = 6.76, 95% (CI 2.15 to 21.2)], multiple gestation [AOR = 1.81, 95% (CI 1.01 to 3.24)] and male gender [AOR = 1.71 95% (CI 1.01 to 2.91)]. CONCLUSION: Nearly three quarters of preterm infants managed at a rural hospital in Uganda had postnatal growth failure. Delayed initiation of enteral feeds and sepsis were highly associated with postnatal growth failure. Enteral feeds should be initiated as soon as possible in these infants to reduce early protein deficits and hence postnatal growth failure.

The Silverman Andersen respiratory severity score in the delivery room predicts subsequent intubation in very preterm neonates.

Treatment with mechanical ventilation is associated with chronic lung disease and poor neurologic outcomes in very premature neonates. Surfactant replacement in patients with respiratory distress syndrome reduces need for mechanical ventilation and may be most beneficial when performed early.

Smoking and its interaction with genetics in MS etiology.

The etiology of multiple sclerosis (MS) involves multifaceted interactions between genetic loci and environmental factors. Smoking is an important risk factor for MS that overall increases the risk of the disease with approximately 50%. However, the precise effects of smoking on MS development vary considerably in different contexts and in different populations. This review focuses on the influence of smoking on MS risk and its interaction with genetics in MS etiology. The possible biological mechanisms are presented in this paper. Further research is needed to establish the mechanisms of causality and to explore preventive strategies.

Do socioeconomic factors affect the prevalence of multiple sclerosis in Iran?

BACKGROUND: A rising trend for incidence of multiple sclerosis (MS) has been observed during the recent years in Iran. Several factors have been investigated as the reason, but socioeconomic determinants have been neglected. The present study aimed to investigate the relationship between Human Development Index (HDI), income and education and MS prevalence in the provinces of Iran. METHODS: The data used in this study were obtained from three sources: (a) National Registry of MS for MS prevalence data from 2006 to 2013, (b) Statistical Centre of Iran for demographic, income, and percentage of educated people data, and (c) some previous studies for HDI data. RESULTS: The findings showed high prevalence of MS in the provinces of Iran. Most patients were residents of provinces with a higher socioeconomic level. Significant relationships were found between the prevalence of MS and HDI, income and educational level (P = .002, P = .006, and P = .001, respectively). CONCLUSION: Socioeconomic determinants in Iran are different from those in many other countries. It seems that Iranian provinces with a higher socioeconomic level have higher prevalence of MS. Further studies in smaller scale are needed to better understand the relationship between socioeconomic determinants and MS prevalence in the provinces of Iran.