Does treatment modality affect measures of arterial stiffness in women with gestational diabetes?

OBJECTIVE: To investigate whether arterial stiffness (AS) differs between healthy women and women with gestational diabetes mellitus (GDM) managed by different treatment modalities. METHODS: This was a prospective longitudinal cohort study comparing AS in pregnancies complicated by GDM and low-risk controls. AS was assessed by recording aortic pulse-wave velocity (AoPWV), brachial augmentation index (BrAIx) and aortic augmentation index (AoAIx) using the Arteriograph® at four gestational-age windows: 24 + 0 to 27 + 6 weeks (W1); 28 + 0 to 31 + 6 weeks (W2); 32 + 0 to 35 + 6 weeks (W3) and ≥ 36 + 0 weeks (W4). Women with GDM were considered both as a single group and as subgroups stratified by treatment modality. Data were analyzed using a linear mixed model on each AS variable (log-transformed) with group, gestational-age window, maternal age, ethnicity, parity, body mass index, mean arterial pressure and heart rate as fixed effects and individual as a random effect. We compared the group means including relevant contrasts and adjusted the P-values using Bonferroni correction. RESULTS: The study population comprised 155 low-risk controls and 127 women with GDM, of whom 59 were treated with dietary intervention, 47 were treated with metformin only and 21 were treated with metformin + insulin. The two-way interaction term of study group and gestational age was significant for BrAIx and AoAIx (P < 0.001), but there was no evidence that mean AoPWV was different between the study groups (P = 0.729). Women in the control group demonstrated significantly lower BrAIx and AoAIx compared with the combined GDM group at W1-W3, but not at W4. The mean difference in log-transformed BrAIx was -0.37 (95% CI, -0.52 to -0.22), -0.23 (95% CI, -0.35 to -0.12) and -0.29 (95% CI, -0.40 to -0.18) at W1, W2 and W3, respectively. The mean difference in log-transformed AoAIx was -0.49 (95% CI, -0.69 to -0.30), -0.32 (95% CI, -0.47 to -0.18) and -0.38 (95% CI -0.52 to -0.24) at W1, W2 and W3, respectively. Similarly, women in the control group also demonstrated significantly lower BrAIx and AoAIx compared with each of the GDM treatment subgroups (diet, metformin only and metformin + insulin) at W1-W3. The increase in mean BrAIx and AoAIx seen between W2 and W3 in women with GDM treated with dietary management was attenuated in the metformin-only and metformin + insulin groups. However, the mean differences in BrAIx and AoAIx between these treatment groups were not statistically significant at any gestational-age window. CONCLUSIONS: Pregnancies complicated by GDM demonstrate significantly higher AS compared with low-risk pregnancies regardless of treatment modality. Our data provide the basis for further investigation into the association of metformin therapy with changes in AS and risk of placenta-mediated diseases. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Frequency of Defecation and Form of Stool among General Bangladeshi Population.

Data on stool form and defecation frequency which are a prerequisite for defining normal bowel habit are lacking in Bangladesh. This observational cross sectional study was designed to find out defecation frequency and stool form among general population in Bangladesh. This study was performed in the Department of Gastroenterology, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh from July 2017 to June 2018. Apparently healthy 1090 respondents were evaluated for predominant stool form (Bristol chart) and frequency. Data on demographic and life-style were collected. The study population consisted of 1090 respondents, among them, 65.13% male and 34.87% female and mean age of them was 40.20±12.39 years. Most of the people 874(80.2%) passed stool between 12-14 times per week followed by 111(10.2%) less than 3 stools per week, 95(8.7%) passed more than 14 stools per week and 10(0.9%) between 3-12 stools per week, p<0.001. Most people passed predominantly Bristol type IV stool- 610(56.0%); followed by type III- 274(25.1%). Other stool forms were: type I- 52(4.8%), type II- 59(5.4%), type V- 31(2.8%), type VI- 33(3.0%), type VII- 31(2.8%), p<0.001. In regard to the physical activity, most of the respondents (70.0%) are physically active whereas about 13.0% are sedentary and about 17.0% are physically intermediate between the two, p<0.001. In the case of dietary habit, most of the participants are non-vegetarian (82.5%) and the remaining are vegetarian (11.1%) and occasional non vegetarian (6.4%), p<0.001. Median stool frequency in the studied population was 14 per week and predominant form was Bristol type IV. Older age was associated with lesser stool frequency, particularly among female subjects.

Knowledge, Attitude and Practice Regarding Environmental Tobacco Smoke among Pregnant Women of Sunsari.

Background Second hand tobacco smoke or Environmental Tobacco Smoke (ETS), contains toxic substances and carcinogens that cause serious health effects in humans. Studies show that ETS exposure during pregnancy is injurious to the mother-infant pair with long term consequences. Limited studies are found in context of ETS in pregnancy in Nepal. Objective To explore the knowledge about harmful effect of ETS exposure in pregnant women and to know the behavior of avoidance from exposure to ETS during pregnancy. Method A cross sectional study was conducted among 303 pregnant women attending antenatal clinics at the District Hospital Inaruwa and BPKIHS Dharan. A pre-tested semi-structured questionnaire was used to collect data regarding socio-demographic characteristics, knowledge, attitude and practice regarding Environmental tobacco smoke. Data was entered in Excel and analyzed in SPSS 11.5. Result The mean age of the respondents was 23.86±4.68 years. The proportion of primigravida was 53.5% and multi-gravida was 46.5%. Among the respondents, 14% were illiterate and 91% were unemployed. A similar proportion of the husbands (12%) were illiterate. Three-fourth (75%) of the respondents lived in joint family. It was found that 86% of their husbands were smokers. There were 61% of pregnant women who had heard about ETS, mainly through television (35%) and radio (30%). There was 86% of the households who had initiated some measures to prevent smoking inside the house. Conclusion The pregnant women in this study are aware about ETS. However a significant number of them believe that ETS is not harmful compared to active smoking. There is a need for further studies to identify interventions to avoid ETS exposure among the pregnant women.

Randomized trial of red cell washing for the prevention of transfusion-associated organ injury in cardiac surgery.

BACKGROUND: Experimental studies suggest that mechanical cell washing to remove pro-inflammatory components that accumulate in the supernatant of stored donor red blood cells (RBCs) might reduce inflammation and organ injury in transfused patients. METHODS: Cardiac surgery patients at increased risk of large-volume RBC transfusion were eligible. Participants were randomized to receive either mechanically washed allogenic RBCs or standard care RBCs. The primary outcome was serum interleukin-8 measured at baseline and at four postsurgery time points. A mechanism substudy evaluated the effects of washing on stored RBCs in vitro and on markers of platelet, leucocyte, and endothelial activation in trial subjects. RESULTS: Sixty adult cardiac surgery patients at three UK cardiac centres were enrolled between September 2013 and March 2015. Subjects received a median of 3.5 (interquartile range 2-5.5) RBC units, stored for a mean of 21 ( sd 5.2) days, within 48 h of surgery. Mechanical washing reduced concentrations of RBC-derived microvesicles but increased cell-free haemoglobin concentrations in RBC supernatant relative to standard care RBC supernatant. There was no difference between groups with respect to perioperative serum interleukin-8 values [adjusted mean difference 0.239 (95% confidence intervals -0.231, 0.709), P =0.318] or concentrations of plasma RBC microvesicles, platelet and leucocyte activation, plasma cell-free haemoglobin, endothelial activation, or biomarkers of heart, lung, or kidney injury. CONCLUSIONS: These results do not support a hypothesis that allogenic red blood cell washing has clinical benefits in cardiac surgery. CLINICAL TRIAL REGISTRATION: ISRCTN 27076315.

Detection of Focal Longitudinal Changes in the Brain by Subtraction of MR Images.

BACKGROUND AND PURPOSE: The detection of new subtle brain pathology on MR imaging is a time-consuming and error-prone task for the radiologist. This article introduces and evaluates an image-registration and subtraction method for highlighting small changes in the brain with a view to minimizing the risk of missed pathology and reducing fatigue. MATERIALS AND METHODS: We present a fully automated algorithm for highlighting subtle changes between multiple serially acquired brain MR images with a novel approach to registration and MR imaging bias field correction. The method was evaluated for the detection of new lesions in 77 patients undergoing cardiac surgery, by using pairs of fluid-attenuated inversion recovery MR images acquired 1-2 weeks before the operation and 6-8 weeks postoperatively. Three radiologists reviewed the images. RESULTS: On the basis of qualitative comparison of pre- and postsurgery FLAIR images, radiologists identified 37 new ischemic lesions in 22 patients. When these images were accompanied by a subtraction image, 46 new ischemic lesions were identified in 26 patients. After we accounted for interpatient and interradiologist variability using a multilevel statistical model, the likelihood of detecting a lesion was 2.59 (95% CI, 1.18-5.67) times greater when aided by the subtraction algorithm (P = .017). Radiologists also reviewed the images significantly faster (P < .001) by using the subtraction image (mean, 42 seconds; 95% CI, 29-60 seconds) than through qualitative assessment alone (mean, 66 seconds; 95% CI, 46-96 seconds). CONCLUSIONS: Use of this new subtraction algorithm would result in considerable savings in the time required to review images and in improved sensitivity to subtle focal pathology.

Late production of CXCL8 in ruminant oro-nasal turbinate cells in response to Chlamydia abortus infection.

Chlamydia abortus is an obligate intracellular bacterium that is an important cause of ovine abortion worldwide. There are reports of abortions in cattle, but these are very rare compared to the reported incidence in sheep. The bacterium is transmitted oro-nasally and can establish a sub-clinical infection until pregnancy, when it can invade the placenta and induce an inflammatory cascade leading to placentitis and abortion. Early host-pathogen interactions could explain differential pathogenesis and subsequent disease outcome in ruminant species. In this study, we assessed the ability of sheep and cattle oro-nasal turbinate cells to sense and respond to C. abortus infection. The cells expressed toll like receptor (TLR) 2, TLR4, nucleotide oligomerization domain (NOD) 1 and NOD-like receptor pyrin domain containing 3 (NLRP3) mRNA. In response to C. abortus infection, both ovine and bovine turbinate cells produce CXCL8 mRNA and protein late in the bacterial developmental cycle, but do not produce IL-1ß or TNF-α. The UV-inactivated bacteria did not elicit a CXCL8 response, suggesting that intracellular multiplication of the bacteria is important for activating the signalling pathways. The production of innate immune cytokines from cattle and sheep turbinate cells in response to C. abortus infection was found to be largely similar.

Selection and characterisation of monepantel resistance in Teladorsagia circumcincta isolates.

Monepantel (MPTL) is one of two new anthelmintic compounds introduced onto the sheep market to control gastro-intestinal nematodes. Resistance to this compound is rare but has been reported. In order to preserve the efficacy of this and other anthelmintics, it is essential to understand both (a) the mechanisms involved in the selection of resistance and (b) how the parasites evolve to deal with these compounds. To address these questions three MPTL-resistant Teladorsagia circumcincta isolates (MTci2-11, MTci5-13 and MTci7-12) have been artificially selected in vivo from phenotypically characterised parent isolates (MTci2, MTci5, MTci7 respectively). The selection process involved collecting and culturing eggs from surviving worms from sheep administered sub-optimal dosages of MPTL (Zolvix®) to provide infective larvae to infect further sheep until resistant isolates were generated (between 9 and 13 rounds of selection). A controlled efficacy test was conducted using the original parental isolates and the newly generated MPTL resistant isolates (n = 5 per group). Selected isolates were assessed both under anthelmintic stress (Zolvix®, 2.5 mg/kg bodyweight; MTci-MPTL) and at rest (untreated, MTci-CON). A number of life-history traits were assessed, namely, worm establishment rates, time to patency, faecal egg output, body length of adults and eggs in utero. The estimated resistance status of the selected isolates was confirmed with 48%, 28% and 9% reductions in worm burden at 7-days post Zolvix® administration for MTci2-11-MPTL, MTci5-13-MPTL and MTci7-12-MPTL, respectively, compared with untreated controls. One of the selected isolates MTci7-12-CON showed significantly greater total worm burden (p = 0.025), greater establishment rate (p = 0.033), decreased time to patency (p = 0.048), higher cumulative egg outputs (p = 0.002) compared with its parental derivative MTci7. The trial results suggest that anthelmintic selection in T. circumcincta, albeit under experimental conditions, can select for more prolific/fecund and quicker maturing populations. These data provide an insight into how parasites evolve in response to anthelmintic pressure.

Regulatory and effector T cells changes in remission and resistant state of childhood nephrotic syndrome.

Idiopathic minimal change disease is a disorder of T-cell dysfunction. The relative predominance of regulatory T cells (Tregs), Th1, and Th2 cells in nephrotic syndrome (NS) remains controversial. Imbalance in peripheral blood regulatory and effector T cells (Teff) are linked to cell mediated immune response and may be associated with steroid response in NS. Peripheral blood CD4 + CD25 + FoxP3 + (Tregs), CD4 + IFN-γ(+) (Th1), and CD4 + IL-4 + (Th2) lymphocytes were analyzed in 22 steroid-sensitive NS (SSNS) patients in sustained remission, 21 steroid-resistant NS (SRNS) and 14 healthy controls. The absolute percentage values and ratio of Th1/Tregs, Th2/Tregs, and Th1/Th2 were compared between SSNS, SRNS and control subjects. The percentage of Tregs was lower in SRNS patients (P = 0.001) compared with that of SSNS and healthy control. The percentage of Th1 cells was higher in SRNS (P = 0.001) compared to that of SSNS patients; however, it was similar to healthy controls (P = 1.00). The percentage of Th2 cells in SRNS (P = 0.001) was higher as compared to SSNS and controls. The ratio of Th1/Treg cells in SRNS (P = 0.001) was higher as compared to SSNS patients and controls. The ratio of Th2/Treg was also higher in SRNS as compared to SSNS and controls. The ratio of Th1/Th2 cells in SSNS, SRNS, and healthy controls were similar. The cytokines secretion complemented the change in different T-cell subtypes in SSNS, SRNS and healthy controls. However, the IFN-γ secretion in healthy controles was low inspite of similar percentage of Th1 cells among SRNS cases. We conclude that greater ratio of Tregs compared to that Th1 and Th2 favor steroid sensitivity and reverse ratio results in to SRNS. The difference in ratio is related to pathogenesis or it can be used as marker to predict steroid responsiveness needs further evaluation.

Prioritizing areas for malaria control using geographical information system in Sonitpur district, Assam, India.

OBJECTIVE: To identify the malaria hot spots at health subcentre level in an endemic district using a geographical information system (GIS). The results will be useful for rapid retrieval of malaria information, and to prioritize malaria control efforts in identified hot spots. STUDY DESIGN: Extraction, analysis and synthesis of relevant data. METHODS: Malaria epidemiological data from 2006 to 2009 were analysed to determine the annual parasitic index, slide positivity rate, annual blood examination rate and Plasmodium falciparum percentage for each health subcentre in the district. Maps were produced using GIS, and integrated to identify the malaria hotspots. RESULTS: Out of 288 health subcentres, GIS identified 10 hot spots at extremely high risk of malaria and 14 hot spots at high risk of malaria. Malaria may flare up in these hot spots whenever favourable transmission conditions arise. Health authorities have been advised to establish control measures in these selected hot spots for timely prevention. CONCLUSION: There is a need for adequate monitoring and allocation of available resources for better interventions in the malaria hotspots. The GIS model used in this study can be used, even at village or cluster level, to pin point the malaria hot spots, and information can be updated and retrieved easily.

Seven strains of mice as potential models of bovine pasteurellosis following intranasal challenge with a bovine pneumonic strain of Pasteurella multocida A:3; comparisons of disease and pathological outcomes.

The gram-negative bacterium Pasteurella multocida causes pneumonic and systemic pasteurellosis in bovids for which vaccines are either unavailable or inadequate. The work assessed whether an intranasal P. multocida challenge in mice might provide a model of infection for future vaccine development work. Clinical, pathological and biochemical responses were compared in seven strains of mice challenged with a virulent bovine pneumonic isolate of P. multocida A:3. Six mouse strains (Porton, CD-1, BALB/c, VM, C57BL/10 and C57BL/6) developed clinical signs of pneumonic disease and variable pneumonic lesions 41-70 h post-infection. In contrast, mouse strain RIII became septicaemic within 36 h post-infection. Concentrations of plasma acute phase proteins and serum lipopolysaccharide increased in all mice after infection, and the main or interaction effect of mouse strain and infection status was statistically significant (P<0.05). Responses in C57BL/10 mice showed close similarity to bovine pneumonic and in RIII mice to bovine systemic pasteurellosis.

A cross sectional investigation of malaria epidemiology among seven tea estates in Assam, India.

In the present investigation, the epidemiology of malaria among seven tea estates of Nagaon and Udalguri districts of Assam, India has been described. A cross-sectional open study was carried out to understand the malaria epidemiology and associated risk factors among the tea tribes during March to September 2009. Out of 1,182 peripheral blood smears examined, 506 found positive for malaria (slide positivity rate, SPR = 42.8) with Plasmodium falciparum as predominant species. Dimakuchi tea estate was having highest SPR (P = 0.0275) and contributed more number of P. falciparum cases (P < 0.00001). Tea estates studied in both Udalguri and Nagaon districts were equally affected and the SPR recorded were 41.75 and 43.32% respectively. 154 malaria cases detected were having 'O' blood group but each blood group was found to have similar susceptibility of acquiring malaria infection (χ(2 ) = 3.603; P = 0.3076) and P. falciparum infection (χ(2 ) = 1.818; P = 0.6110). The SPR was highest among children more than 2 years of age group and variation in SPR among the age groups was statistically significant (χ(2 ) = 17.186; P = 0.0018). No gender biasing was observed in malaria distribution. Anemia was found associated with the infection among both the sexes. The findings suggest that tea estates are endemic for stable malaria transmission primarily due to P. falciparum and the prevalence rate decline with age, suggesting the development of protective immunity. Promising intervention measures could be able to reduce the malaria prevalence effectively in the study areas.

Lack of evidence for an association between MHC diversity and the development of bovine neonatal pancytopenia in Holstein dairy cattle.

Bovine neonatal pancytopenia (BNP), a disease of neonatal calves, has been described in a number of European countries since 2006. The disease results in high mortality of calves aged 1-4 weeks and is characterised by severe bone marrow pathology resulting in profound thrombocytopenia and consequent haemorrhagic diathesis. A number of hypotheses including a novel virus infection, plant toxins, a vaccine associated isoimmune disease, or a genetic defect have been suggested to explain the aetiology of this disease. However, as the number of cases in affected herds remains small, it is hypothesised that the genetic background of the calf may influence disease susceptibility. To test this we focused on the class II region of the major histocompatibility complex (MHC) which is often associated with variations in immune response and susceptibility to antibody mediated autoimmune disease. Forty-three cases of BNP and sixty-eight controls were genotyped at the polymorphic class II MHC-DRB3 locus. Twenty DRB3 alleles were identified with seven appearing at frequencies ≥ 0.05. A comparison of the allelic frequencies between diseased and control groups showed that there was no evidence for any significant differences, suggesting that the MHC does not appear to be a predisposing risk factor in the development of BNP in Holstein dairy cattle.

The development of immune responses in Balb/c mice following inoculation with attenuated or virulent Neospora caninum tachyzoites.

Balb/c mice were inoculated intraperitoneally (i.p.) with either 5 x 10(6) live virulent (group 1) or 5 x 10(6) live attenuated (group 2) tachyzoites, or Vero cells (group 3). Animals were killed at 0, 14, 28 and 42 days post-inoculation (p.i.), with the remaining mice receiving a lethal challenge on day 48 p.i. Serum, spleen and brain samples were collected post-mortem to examine humoral and cell-mediated immune responses as well as pathological lesions and to quantify parasite loads. On day 14 p.i. group 2 (attenuated) demonstrated statistically significant (P < 0.001) lower levels of mean morbidity and weight loss, while also showing significantly (P = 0.01) higher levels of splenocyte proliferation and IFN-gamma production (P = 0.003), compared to group 1 (virulent). Histology of brain samples showed milder lesions and a lower incidence of positive immunohistochemistry, demonstrating tachyzoites and tissue cysts, and statistically significant (P = 0.03) lower mean burdens of parasite DNA in group 2 (attenuated) compared to group 1 (virulent). All mice in group 2 were protected following challenge on day 48 p.i. whereas naïve control mice succumbed to the challenge. No mice from group 1 (virulent) survived beyond day 24 p.i. so they were not included in the challenge.

Disseminated intravascular coagulation complicating HELLP syndrome: perioperative management.

HELLP syndrome may lead to disseminated intravascular coagulation (DIC) which can make emergency surgery a serious challenge. A 29-year-old female presented with haematuria, epistaxis and hypertension in the emergency ward and a diagnosis of DIC complicating HELLP in preeclampsia was made. She had continuous epistaxis and elective tracheal intubation was carried out. During emergency caesarean section the patient was managed with blood products, antihypertensive drugs and general anaesthesia together with invasive monitoring. She required postoperative ventilatory support. HELLP syndrome may progress to DIC in 15-38% of patients. The prothrombin time, activated partial thromboplastin time and serum fibrinogen levels are normal in HELLP syndrome but are prolonged in DIC. Evaluation of more sensitive markers of DIC, such as antithrombin III, α-2 antiplasmin, plasminogens, fibrin monomer and D-dimers, differentiates DIC from HELLP syndrome. Aggressive treatment is indicated and delivery should be expedited, by caesarean section if necessary although vaginal delivery is not contraindicated, along with control of blood pressure and coagulation abnormality. We conclude that patients with DIC complicating HELLP syndrome and preeclampsia require great vigilance and multimodal management in the perioperative period for uneventful outcome.

Assessment of the dynamics of microparasite infections in genetically homogeneous and heterogeneous populations using a stochastic epidemic model.

The aim of this paper was to explore the effect of genetic heterogeneity in host resistance to infection on the population-level risks and outcomes of epidemics. This was done using a stochastic epidemiological model in which the model parameters were assumed to be genetically controlled traits of the host. A finite locus model was explored, with a gene controlling the transmission coefficient (i.e., host susceptibility to infection) and a gene controlling the recovery period. Both genes were simulated to have 2 alleles with underlying additive or dominance inheritance and an independent assortment of alleles. The model was parameterized for a viral pig disease (transmissible gastroenteritis), and complete homogeneous mixing among genotypes was assumed. Mean population genotype dramatically affected epidemic outcomes, and subtle effects of heterogeneity on epidemic properties were also observed. Genetic variation in the transmission coefficient led to probabilities of epidemics occurring that were slightly greater than expected, but genetic variation in the recovery rate had no such effect. Epidemics were generally less severe in genetically heterogeneous populations than expected from the constituent subpopulations. Furthermore, the genotype of the initial infected animal had a marked effect on epidemic probabilities, particularly when genetic variation was for recovery rate. The results of this model provide useful information to determine the optimum population structures and to exploit genetic variation in resistance to infection. Applications of the proposed model in genetically heterogeneous populations for identifying practical disease management strategies are also discussed.

Differential expression of inducible nitric oxide synthase and cytokine mRNA in chicken lines divergent for cutaneous hypersensitivity response.

Phytohemagglutinin (PHA)-induced delayed-type hypersensitivity is an immunocompetent trait considered an indicator of cell-mediated immune or T-cell responses. Divergent selection was performed to generate high and low lines for response to PHA-P. Extreme-responder birds of the F2 generation in each line were used to study possible differences in macrophage activity and the associated functional genes. To evaluate macrophage activity, nitric oxide (NO) was estimated both systemically in serum and in in vitro monocyte culture. Semi-quantitative RT-PCR was used to detect the differential mRNA expression patterns of iNOS and MIP-1beta in monocyte culture, whereas T(H)1 cytokines (IL-2 and IFN-gamma) were studied in peripheral blood mononuclear cells (PBMC) at different time intervals after lipopolysaccharide (LPS) induction. The high line showed strong systemic, as well as in vitro NO production, compared to the low line, upon stimulation with NDV and LPS, similar to early and high iNOS mRNA expression. Following the pattern of iNOS gene expression, an early strong expression of cytokines with powerful iNOS-inducing action, such as IFN-gamma and the chemokine MIP-1beta, was observed in the high line. In contrast, for response to PHA-P, low expression of IL-2 was observed in the high compared to the low line. In conclusion, the study revealed that divergent selection for response to PHA-P resulted in a divergent effect on T(H)1 cell activity, resulting in altered macrophage function in chickens. Selection, based on response to PHA-P, could lead to more resistant birds or birds with an enhanced immune response.