Association of Virulence Markers With Resistance to Oral Antibiotics in Escherichia coli Isolates Causing Uncomplicated Community-Acquired Cystitis.

INTRODUCTION: Uropathogenic Escherichia coli (UPEC) strains equipped with putative virulence factors (VFs) are known to cause approximately 90% of lower urinary tract infections (UTIs) or cystitis affecting individuals of all age groups. Only limited laboratory-based data on the correlation of antimicrobial resistant patterns and VFs of UPEC are available. MATERIALS AND METHODS: A total of 100 non-duplicate E. coli isolates associated with community-acquired UTIs in sexually active women were analysed for antimicrobial susceptibility patterns and putative virulence-associated genes. Antimicrobial susceptibility testing (AST) was carried out by the Kirby-Bauer disk diffusion method, and results were interpreted as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The isolates non-susceptible to ≥1 agent in ≥3 different antimicrobial categories were considered multidrug-resistant (MDR). Multiplex polymerase chain reaction assay was performed on each E. coli isolate to characterize putative virulence genes (VGs) such as papA, malX, PAI, ibeA, fimH, fyuA, sfa/focDE, papGIII, iutA, papGI, kpsMTII, hlyA, papGII, traT, afa/draBC, cnf1, vat, and yfcV. Results: Capsule synthesis gene kpsMTII (59%)was the most predominant VG present, followed by serum resistance-associated transfer protein gene traT (58%) and adhesin gene fimH (57%); however, adhesin gene papGI (2%) was the least present. The prevalence of antimicrobial resistance was relatively high for commonly used oral antimicrobials of UTI treatment, such as trimethoprim-sulfamethoxazole (68%) and fluoroquinolones (63%). The majority of isolates were MDR (78%) and resistant to extended-spectrum cephalosporins (63.5%). Isolates resistant to norfloxacin and trimethoprim-sulfamethoxazole were also resistant to almost all available oral antimicrobials. Isolates resistant to extended-spectrum cephalosporins showed increased resistance to aztreonam and trimethoprim-sulfamethoxazole (84.6% each) and fluoroquinolones (ciprofloxacin and norfloxacin; 81.5% each). Fosfomycin and nitrofurantoin were the most sensitive antimicrobials for all these resistant isolates. In a multivariate analysis, it was found that MDR isolates were associated with many of the VGs; fimH (65.4%) being the most frequent followed by traT (64.1%). traT (66.2%) and iutA (60.3%) were most commonly present in E. coli isolates resistant to trimethoprim-sulfamethoxazole, while66.7% norfloxacin-resistant isolates have them. Isolates resistant to extended-spectrum cephalosporins were most commonly associated with fimH and traT (66.2% each). However, E. coli isolates positive for sfa/focDE and vat were more sensitive to norfloxacin and trimethoprim-sulfamethoxazole and were non-MDR strains predominantly (p < 0.05). Only two VGs (fimH and traT) were significantly associated with MDR strains. DISCUSSION: The results of the present study clearly show the association of VFs with some of the commonly used oral antibiotics emphasizing the need for further molecular studies and surveillance programs to monitor drug-resistant UPEC so as to form optimized diagnostic stewardship and appropriate regimen for patient treatment. The reason behind this phenomenon of association has not been studied in much detail here but it can be assumed that genes responsible for drug resistance may share neighbouring loci with VGs on the mobile genetic elements (e.g., plasmid), which transfer together from one bacterium to another.

Can Medical Nutrition Therapy Affect Feto-Maternal Outcomes in Gestational Glucose Intolerance: An Open-Label Pilot Randomized Control Trial in World's Diabetes Capital.

Introduction: Gestational diabetes is defined as the carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Gestational glucose intolerance (GGI) is used to indicate pregnant women whose 2-h postprandial glucose is > 120 mg/dl and below 140 mg/dl (Diabetes in Pregnancy Study Group of India, DIPSI criteria). Aim: This study was planned to see whether intervention in GGI group helps to improve feto-maternal outcomes. Methodology: This open-label randomized control trial was conducted in Department of Obstetrics and Gynaecology of King George's Medical University, Lucknow. Inclusion criteria were all the antenatal women attending the antenatal clinic and diagnosed as GGI, and exclusion criteria were overt diabetes. Results: Total of 1866 antenatal women were screened, and among them, 220 (11.8%) women were diagnosed as gestational diabetes; 412 (22.1%) women were diagnosed as GGI. The mean fasting blood sugars in the women with GGI who had medical nutrition therapy were much lower than the women with GGI who did not have any intervention. The present study showed the women with GGI had higher complications like polyhydramnios, PPROM, foetal growth restriction, macrosomia, preeclampsia, preterm labour and vaginal candidiasis more in the women with GGI as compared to euglycaemic women. Conclusion: The present study of nutritional intervention in GGI group has shown trend towards lesser complication if we start medical nutrition therapy reflected by delayed development of GDM and less neonatal hypoglycaemia and hyperbilirubinemia.

Psychometric validation of the hindi version of summary of diabetes self-care activities (H-SDSCA) amongst pregnant women with gestational diabetes mellitus, in Lucknow.

Objective: The English version of the Summary of Diabetes Self-Care Activities (SDSCA) measure is the most often used self-reporting instrument assessing diabetes self-management. This study was aimed at translating English SDSCA into the Hindi version and validating and evaluating its psychometric properties. Methods: The Hindi version of SDSCA was developed based on the guidelines provided by the World Health Organization (2008) for translation and adaptation of tool. Following steps were adopted: (1) Cultural and linguistic validation, (2) content validity testing, (3) construct validity testing, and (4) internal validity testing. Sixty women diagnosed with GDM were selected for the purpose of this study. Results: The tool showed promising and satisfactory results. Of mention are the results related to Cronbach's alpha (0.82). The exploratory factor analysis showed three factors that fit the data satisfactorily. Conclusions: This study provided evidence for the reliability and validity of the Hindi Summary of Diabetes Self-Care Activities instrument, which may be used in the future to assess diabetes self-management activities among the pregnant women diagnosed with gestational diabetes mellitus among Hindi-speaking population.

Association of long and short interpregnancy intervals with maternal outcomes.

Background: Interpregnancy interval (IPI) is spacing between live birth and beginning a new pregnancy. Both long and short IPIs have been associated with adverse maternal outcomes. There is paucity in the Indian literature regarding the impact of IPI on maternal outcomes. Materials and Methodology: The cross-sectional study was conducted in the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, from July 2019 to June 2020. Women with previous abortions, previous stillbirth, nulliparity, or multiple pregnancies were excluded. A pre-structured pro forma was used for demographic details. IPI was categorized as <6 months, 6 to <24 months, 24 to <60 months, and 60 months. Maternal outcomes were studied, and odds ratios were calculated. Results: There were 6984 deliveries in the period. A total of 4812 women were enrolled after following the inclusion and exclusion criteria. Of 4812 women, 142 (2.9%) had IPI <6 months, 3336/4812 women (69.3%) had IPI 6 to <24 months, 1144/4812 women (23.7%) had IPI 24 to <60 months, and 3.9% women (190/4812) had IPI ≥60 months. High risk of fetal malposition (OR 3.84), fetal growth restriction (OR 2.06), and hypertension (OR 1.86) were seen in women with short IPI <6 months. Women with longer IPI (≥ 60 months) had higher chances of preterm labor (OR 3.82), oligoamnios (OR 2.54), gestational diabetes (OR 2.19), and anemia (OR 1.45). Conclusion: Three-fourths of women had IPI less than 24 months recommended as minimum interval by WHO. Efforts are needed to increase awareness and availability of contraceptive choices for postpartum women to ensure adequate spacing.

Analysis of Causes of Hepatic Dysfunction in Obstetric Patients in India: A Systematic Review.

BACKGROUND: Epidemiology of liver disease in obstetric patients shows geographical variation depending upon the prevalence of preeclampsia, viral hepatitis, and tropical vector-borne diseases like malaria, leptospirosis, etc. We undertook the current systematic review to analyze the causes of hepatic dysfunction in obstetric patients in India and identify the gaps in the literature and reporting. MATERIALS AND METHODS: We did a systematic review of studies reporting the causes of hepatic dysfunction in obstetric patients in India. A methodological quality assessment was done using a five-point questionnaire. RESULTS: A total of 21 studies qualified for evaluation. The rate of hepatic dysfunction among obstetric patients in India ranged from 0.15 to 3.3% with a mean and median rate of 1.49 and 0.93%, respectively. Preeclampsia/HELLP (mean = 36.0%, median = 31.4%, range: 3.6-83.8%) and viral hepatitis (mean = 34.1%, median = 35.5%, range: 5.1-61.8%) were the commonest causes of hepatic dysfunction. Other causes were intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, tropical fever (malaria, leptospirosis, dengue, scrub typhus), etc. Maternal mortality ranged from 1.4 to 40% (mean = 12.6%, median = 10.0%) and perinatal mortality was between 16.4 and 38.70% (mean = 31.75%, median = 35.5%). CONCLUSION: There is moderate quality evidence to show that preeclampsia/HELLP and viral hepatitis are the commonest causes of hepatic dysfunction in obstetric patients in India. HOW TO CITE THIS ARTICLE: Ahmed A, Saxena S, Pandey A, Mishra P, Azim A. Analysis of Causes of Hepatic Dysfunction in Obstetric Patients in India: A Systematic Review. Indian J Crit Care Med 2022;26(1):114-122.

Vaginal probiotics as an adjunct to antibiotic prophylaxis in the management of preterm premature rupture of the membranes.

Preterm birth is a leading cause of perinatal morbidity and mortality and Preterm premature rupture of the membranes (PPROM) is a major risk factor contributing to approximately one third of preterm deliveries. Vaginal infections are often associated with PPROM and are characterised by loss of lactobacillin normal vaginal flora and overgrowth of other pathogenic microorganisms. Probiotics appear to have an emerging role in prolonging pregnancy after PPROM. This trial compared the efficacy of a vaginal probiotic in combination with standard antibiotic prophylaxis versus only antibiotic in prolongation of latency period and on perinatal outcome in cases of PPROM between 24 and 34 weeks. Although no significant difference was observed in the mean latency period (p = 0.937) and mean gestational age at birth (p = 0.863) between the two groups, the overall neonatal outcome was better in the study group. There is need of further large-scale clinical trials to demonstrate effectiveness of probiotics.IMPACT STATEMENTWhat is already known on this subject? PPROM is an important cause of preterm birth. Prematurity leads significant global burden of neonatal morbidity and mortality. Antibiotics in PPROM have a proven benefit to prolong latency period from start of PPROM to birth. Probiotics have a role in improving vaginal flora and reducing infections and have been tried in PPROM.What do the results of this study add? The usefulness of probiotics in prolonging latency period and improving neonatal outcome has been reported in limited trials. In our study it has shown an improvement in neonatal outcome overall but not statistically significant compared to few studies which have reported significant beneficial effects. This might be due to existence of variation in the type of the vaginal microflora in different study population.What are the implications of these findings for clinical practice and/or further research? Preliminary results suggest that use of probiotic may benefit women with PPROM. This also implies need of multicentric larger scales trials with different types of probiotics so as to clarify whether any intervention in vaginal microflora can lead to any benefits in reducing the prematurity and its consequence, both on the neonate and heath care infrastructure.

Enhancing Cohort PASA Efficiency from Lessons Assimilated by Mutant Genotyping in C. elegans.

Classical restriction fragment length polymorphism (RFLP) and sequencing are labor-intensive and expensive methods to study single base changes, whereas polymerase chain reaction amplification of specific alleles (PASA) or allele-specific polymerase chain reaction (ASPCR) is a PCR-based application that allows direct detection of any point mutation by analyzing the PCR products in an ethidium bromide-stained agarose or polyacrylamide gel. PASA is based on oligonucleotide primers containing one or more 3' mismatch with the target DNA making it refractory to primer extension by Thermus aquaticus DNA polymerase lacking the 3' to 5' exonuclease proofreading activity because of which it is also called amplification refractory mutation system-PCR (ARMS-PCR). This technique has found application in detection of allele, mutation, single-nucleotide polymorphisms (SNPs) causing genetic and infectious diseases. This chapter describes an approach of cohort PASA in context of genotyping single and double mutant worms generated to study the process of cell migration and axon outgrowth in C. elegans. Single worm-based cohort PASA allows genotyping for identification of single base mutations; particularly it is convenient method to detect mutations without a visible phenotype.

The Potential Role of Plastome Copy Number as a Quality Biomarker for Plant Products using Real-time Quantitative Polymerase Chain Reaction.

Background: Plastids are plant-specific semi-autonomous self-replicating organelles, containing circular DNA molecules called plastomes. Plastids perform crucial functions, including photosynthesis, stress perception and response, synthesis of metabolites, and storage. The plastome and plastid numbers have been shown to be modulated by developmental stage and environmental stimuli and have been used as a biomarker (identification of plant species) and biosensor (an indicator of abiotic and biotic stresses). However, the determination of plastome sequence and plastid number is a laborious process requiring sophisticated equipment. Methods: This study proposes using plastome copy number (PCN), which can be determined rapidly by real-time quantitative polymerase chain reaction (RT-qPCR) as a plant product quality biomarker. This study shows that the PCN log10 and range PCN log10 values calculated from RT-qPCR data, which was obtained for two years from leaves and lint samples of cotton and seed samples of cotton, rice, soybean, maize, and sesame can be used for assessing the quality of the samples. Results: Observation of lower range PCN log10 values for CS (0.31) and CR (0.58) indicated that the PCN showed little variance from the mean PCN log10 values for CS (3.81) and CR (3.85), suggesting that these samples might have encountered ambient environmental conditions during growth and/ or post-harvest storage and processing. This conclusion was further supported by observation of higher range PCN log10 values for RS (3.09) versus RP (0.05), where rice seeds in the RP group had protective hull covering compared to broken hull-less seeds in the RS group. To further support that PCN is affected by external factors, rice seeds treated with high temperatures and pathogens exhibited lower PCN values when compared to untreated seeds. Furthermore, the range PCN log10 values were found to be high for cotton leaf (CL) and lint (Clt) sample groups, 4.11 and 3.63, respectively, where leaf and lint samples were of different sizes, indicating that leaf samples might be of different developmental stage and lint samples might have been processed differently, supporting that the PCN is affected by both internal and external factors, respectively. Moreover, PCN log10 values were found to be plant specific, with oil containing seeds such as SeS (6.49) and MS (5.05) exhibiting high PCN log10 values compared to non-oil seeds such as SS (1.96). Conclusion: In conclusion, it was observed that PCN log10 values calculated from RT-qPCR assays were specific to plant species and the range of PCN log10 values can be directly correlated to the internal and external factors and, therefore might be used as a potential biomarker for assessing the quality of plant products.

Etiology of Pregnancy-related Acute Kidney Injury among Obstetric Patients in India: A Systematic Review.

Background: Pregnancy-related acute kidney injury (PRAKI) is an important cause of fetomaternal mortality and morbidity in developing countries. We undertook a systematic review to identify the causes of PRAKI among obstetric patients in India. Materials and methods: We systematically searched PubMed, MEDLINE, Embase, and Google Scholar using appropriate search terminology between 1 January 2010 to 31 December 2021. Studies reporting the etiology of PRAKI among obstetric patients (pregnant and within 42 days postpartum) in India were included for evaluation. Studies done in any other geographical location besides India were excluded. We also excluded studies done in any one trimester or any specific subgroup of patients [e.g., postpartum acute kidney injury (AKI), postabortal AKI]. A five-point questionnaire was used to assess the risk of bias in included studies. The results were synthesized as per preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: A total number of 7 studies with 477 participants were included for analysis. All were single-center descriptive observational studies either done in tertiary care public or private hospitals. Sepsis (mean, 41.9%; median, 49.4%; and range, 6-56.1%) was the most common cause of PRAKI followed by hemorrhage (mean, 22.1%; median, 23.5%; and range, 8.3-38.5%) and pregnancy-induced hypertension (mean, 20.9%; median, 20.7; and range, 11.5-39%). Among these seven studies, five were of moderate quality, one was of high quality, and another one was of low quality. Our study is limited due to the lack of consensus definition of PRAKI in literature and heterogeneity in reporting methods. Our study highlights the need for a structured reporting format for PRAKI to understand the true disease burden and take control measures. Conclusion: There is a moderate quality of evidence to suggest that sepsis followed by hemorrhage and pregnancy-induced hypertension are the commonest causes of PRAKI in India. How to cite this article: Gautam M, Saxena S, Saran S, Ahmed A, Pandey A, Mishra P, et al. Etiology of Pregnancy-related Acute Kidney Injury among Obstetric Patients in India: A Systematic Review. Indian J Crit Care Med 2022;26(10):1141-1151.

Midterm eGFR Predicts Pregnancy Outcomes: An Observational Study.

INTRODUCTION: The hemodynamic adjustments during pregnancy play a pivotal role in sustaining the gestation, however, its clinical connotation on midterm renal hyperfiltration and its consequence on maternal and fetal outcomes need a greater appraisal. The present retrospective study looked into the midterm estimated glomerular filtration rate (eGFR) among pregnant females without overt pieces of evidence of chronic kidney disease (CKD) as a surrogate marker for midterm hyperfiltration and its implication on maternal and fetal outcomes. MATERIALS AND METHODS: All pregnancies among females aged 18-50 years with available pregestational baseline serum creatinine were included in the study. Maternal renal hyperfiltration was expressed as the highest eGFR, using the creatinine clearance method. Its association with adverse maternal and fetal outcomes was assessed. RESULTS: A total of 1,045 pregnancies were assessed during the study. According to midterm eGFR, among them, 65% of pregnancies showed midterm eGFR between 120 and 150, however, 4.3% of pregnancies had values more than 150 mL/min per 1.73 m2 . The risk of poor pregnancy outcome was observed for eGFR levels below and above the reference level of 120-150 mL/min per 1.73 m2 (1.97 for values ≥150 mL/min per 1.73 m2 , and 1.72 for 90-120 mL/min per 1.73 m2 ). Pregnancies with eGFR between 60 and 90 mL/min per 1.73 m2 had odds ratios (ORs) of 5.64. CONCLUSION: A distinctive relationship was observed between the midterm eGFR and adverse pregnancy outcomes with the best outcomes for midterm eGFR levels between 120 and 150 mL/min per 1.73 m2 . Despite no apparent functional renal deterioration, a poor maternal hyperfiltration response may play a crucial impact on poor pregnancy outcomes.

Correlation of Insulin Resistance in Pregnancy with Obstetric Outcome.

INTRODUCTION: Pregnancy is characterized by a series of metabolic changes that promote insulin resistance. This could be due to increase in the plasma levels of one or more pregnancy-related hormones such as oestrogen, progesterone, prolactin, cortisol, and human placental lactogen (HPL). The increased insulin resistance in pregnancy is associated with development of diabetes which has implications for the future gestations also. AIMS AND OBJECTIVES: To determine status of insulin resistance in pregnant women and correlate the presence of insulin resistance with obstetric outcome. MATERIAL AND METHOD: A prospective cohort study was conducted in the Department of Obstetrics and Gynaecology, KGMU, Lucknow, over a period of one year. Total 150 pregnant women were enrolled from OPD, out of which 136 women were followed up till delivery. Insulin resistance was calculated by HOMA IR index, twice in whole antenatal period (first in early pregnancy and second in late pregnancy). All women were also tested for GDM by DIPSI test (plasma glucose value after 2 h of 75 gm glucose load irrespective of last meal) as per protocol. RESULTS: In our study, we found 71 women out of 136 (52.2%) were GDM. Total 30 women out of 136 (22.05%) were GGI (Gestational Glucose Intolerance), and total 38 out of 136 (27.9%) women were found to have insulin resistance using HOMA IR ≥ 2 as cut off. Significant correlation was found in between BMI and insulin resistance (p = 0.001) and between GDM and insulin resistance (p = 0.001). Relative risk of development of complications like Preeclampsia, neonatal hypoglycemia, and respiratory distress syndrome was higher in women having insulin resistance and GDM. CONCLUSION: Obstetric complications like preeclampsia, neonatal hypoglycemia, and respiratory distress syndrome are more likely to occur in women with insulin resistance, but larger studies are required to delineate whether insulin resistance alone without development of GDM will have the same implication.

Pregnancy in women with previous two healthy children, associated factors, and acceptability of contraception among these women: A questionnaire-based, cross-sectional KAP study in world's second most populated country advocating two-child norm.

INTRODUCTION: Indian subcontinent carries 17 % of world's population, being the second largest populated country. The maternal mortality rate of the country is still high. The study was aimed to study factors leading to pregnancy in women with previous two living children and their knowledge about limiting family and their practice for use of contraceptives. METHODS: Questionnaire-based study was conducted in the Department of Obstetrics and Gynaecology. RESULTS: 961 pregnant women attending antenatal outpatient department were interrogated and amongst them 167 (17.3 %) multigravida with previous two healthy children were enrolled in study and were asked to document in Questionnaire. Reasons for current pregnancy were gender bias, no desire to limit family, incorrect contraceptive use, contraceptive failure, doctor's mistake and religious belief. Desire for male child emerged as most common reason (37%) followed by improper or no use of contraception. Most significant associated factor was poor education of female partner (p = 0.010). CONCLUSION: This cross-sectional study evaluated the possible reasons of multiparity. We conclude that preference for male gender child is still very much prevalent in India, along with unmet need of family planning. Improving education of women might help to change attitude towards birth spacing and family size.

Pilot Interventional Study Comparing Fetomaternal Outcomes of 150 mg Versus 75 mg Aspirin Starting Between 11 and 14 Weeks of Pregnancy in Patients with High Risk of Preeclampsia: A Randomized Control Trial.

INTRODUCTION: Hypertensive disorders of pregnancies complicate around 5-10% of pregnancies worldwide, and together they are a member of the deadly triad along with haemorrhage and infection that contribute to a significant amount of maternal morbidity and mortality. AIMS AND OBJECTIVES: To compare differences in the fetomaternal outcomes with the use of 150 mg aspirin versus 75 mg aspirin in pregnant women found to be at high risk of PE. METHODOLOGY: This was a two-armed double-blind parallel randomized control trial conducted in the Department of Obstetrics and Gynaecology, King George's Medical University, carried over a period of 1 year. RESULTS: Preeclampsia occurred in 15 of 87 participants (17%) in the 75 mg aspirin group compared with 6 of 91 (6.5%) in the 150 mg aspirin group. There were a significantly higher incidence of PE, its severity and lesser period of gestation at delivery in the group given 75 mg dose compared to the group given 150 mg dose. There were significantly higher values of mean arterial pressure and uterine artery PI in women who developed preeclampsia compared to those who do not in both the groups. Foetal outcomes were observed in both the groups of women, and there was no statistically significant difference between them. CONCLUSION: This randomized trial showed that among women with singleton pregnancies who were identified by means of first-trimester screening as being at high risk of preterm preeclampsia, use of aspirin 150 mg per day started between 11 and 14 weeks till 36 weeks is a potent intervention to reduce the development of both early- and late-onset preeclampsia as compared to a dose of 75 mg per day.

Clinical correlation of molecular (VEGF, FGF, PDGF, c-Myc, c-Kit, Ras, p53) expression in juvenile nasopharyngeal angiofibroma.

BACKGROUND: A molecular surrogate may exist for the clinical behaviour of juvenile nasopharyngeal angiofibroma (JNA). METHODS: In 9-14 cases, a 'correlation' of clinical behaviour with molecular expression (m-RNA expression through RT-PCR) of VEGF, FGF, PDGF, Ras, c-Myc, c-Kit and p53 was undertaken. RESULTS: A comparison of the two extremes of expressions characterized some specific clinical phenotypes for every marker except c-Myc. A higher FGF was associated with post-adolescent presentation, smaller tumour size, enhanced haemorrhage and recurrence. A higher c-Kit was associated with adolescents, rapid growth, skull base involvement and recurrence. Enhanced Ras was associated with post-adolescence, smaller tumour size, skull base involvement and recurrence. Enhanced p53 and PDGF were associated with adolescents, early presentation and rapid progression. Higher VEGF expression was associated with skull base involvement and enhanced haemorrhage. CONCLUSION: This study is currently the only evidence revealing a clinical molecular association in JNA and larger multicentric studies need to be performed to show a statistical significance.

A protein phosphatase 2C, AP2C1, interacts with and negatively regulates the function of CIPK9 under potassium-deficient conditions in Arabidopsis.

Potassium (K+) is a major macronutrient required for plant growth. An adaptive mechanism to low-K+ conditions involves activation of the Ca2+ signaling network that consists of calcineurin B-like proteins (CBLs) and CBL-interacting kinases (CIPKs). The CBL-interacting protein kinase 9 (CIPK9) has previously been implicated in low-K+ responses in Arabidopsis thaliana. Here, we report a protein phosphatase 2C (PP2C), AP2C1, that interacts with CIPK9. Fluorescence resonance energy transfer (FRET), bimolecular fluorescence complementation (BiFC), and co-localization analyses revealed that CIPK9 and AP2C1 interact in the cytoplasm. AP2C1 dephosphorylates the auto-phosphorylated form of CIPK9 in vitro, presenting a regulatory mechanism for CIPK9 function. Furthermore, genetic and molecular analyses revealed that ap2c1 null mutants (ap2c1-1 and ap2c1-2) are tolerant to low-K+ conditions, retain higher K+ content, and show higher expression of K+-deficiency related genes contrary to cipk9 mutants (cipk9-1 and cipk9-2). In contrast, transgenic plants overexpressing AP2C1 were sensitive to low-K+ conditions. Thus, this study shows that AP2C1 and CIPK9 interact to regulate K+-deficiency responses in Arabidopsis. CIPK9 functions as positive regulator whereas AP2C1 acts as a negative regulator of Arabidopsis root growth and seedling development under low-K+ conditions.

Torsion and rupture of a non-communicating rudimentary horn in a 17-week gestation in a 16-year-old girl: lessons learnt.

A unicornuate uterus with non-communicating rudimentary horn has always been notorious and poses threat to continuation of pregnancy with dismal consequences. We are reporting an interesting case of uterine malformation with a 90° rotation of uterine axis which ultimately ruptured during termination of pregnancy. The rarity in our case was not only conception in non-communicating horn but also the complete twisting of axis which made the pregnant horn come in front of the non-gravid unicornuate uterus, mimicking normal pregnancy. The most important lesson learnt is that if induction does not lead to cervical changes and uterine contractions, one must consider atypical presentations of an anomalous uterus as a possible differential before proceeding further.

The unc-53 gene negatively regulates rac GTPases to inhibit unc-5 activity during Distal tip cell migrations in C. elegans.

The unc-53/NAV2 gene encodes for an adaptor protein required for cell migrations along the anteroposterior (AP) axes of C. elegans. This study identifies unc-53 as a novel component of signaling pathways regulating Distal tip cell (DTC) migrations along the AP and dorsoventral (DV) axes. unc-53 negatively regulates and functions downstream of ced-10/Rac pathway genes; ced-10/Rac and mig-2/RhoG, which are required for proper DTC migration. Moreover, unc-53 exhibits genetic interaction with abl-1 and unc-5, the 2 known negative regulators of ced-10/Rac signaling. Our genetic analysis supports the model, where abl-1 negatively regulates unc-53 during DTC migrations and requirement of unc-53 function during both AP and DV DTC migrations could be due to unc-53 mediated regulation of unc-5 activity.

Aberrant Akt Activation During Implantation Window in Infertile Women With Intramural Uterine Fibroids.

The objective of the study was to examine the expression and cellular distribution of key signaling components of the phosphatidylinositol-3-kinase (PI3K)/Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Protein Kinase B (PKB/Akt) pathway during the window of implantation in infertile women with noncavity-distorting intramural uterine fibroids (n = 21) as compared to fertile controls (n = 15). Relative gene expression analysis of PIK3CA, PTEN, Akt1, and Akt2 genes in midluteal endometrial biopsies was performed by real-time polymerase chain reaction. Immunohistochemistry was used to evaluate the expression of PIK3CA, PTEN, phospho-PTEN, Akt1, Akt2, phospho-Akt1 (serine 473), phospho-Akt1 (threonine 308), and Ki67 proteins. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay was performed for apoptosis detection. In comparison to fertile controls, significant upregulation of Akt1 messenger RNA levels (2.16-fold; P < .05); cell-specific upregulation of the proteins phospho-PTEN ( P < .05), Akt1 ( P < .05), Akt2 ( P < .05), and p-Akt (S473; P < .001); and downregulation of PTEN ( P < .01) were observed in endometrium of infertile women with intramural fibroids. The ratio of p-PTEN/PTEN and p-Akt1 (S473)/Akt1 was also significantly higher in infertile women. Increased Ki67 labeling index in the glandular epithelium and significantly lower apoptotic index in glandular epithelium and stroma were seen in infertile women during the window of implantation. Aberrant Akt activation and the associated imbalance in endometrial proliferation and apoptosis observed in infertile women with intramural fibroids during the midsecretory phase might contribute to impaired endometrial receptivity leading to infertility in these patients.