The Prevalence and Risk Factors of Pregnancy-Related Anxiety in Bahrain.

Objectives We aim to estimate the prevalence of anxiety among pregnant women, explore the possible risk factors, and compare the presence of anxiety in each gestational trimester in all pregnant women attending the antenatal care clinics at a tertiary care hospital in Manama, Bahrain. Methods This study followed a cross-sectional research design at the antenatal clinics of Salmaniya Medical Complex in Manama, Bahrain. Direct interviews with 513 participants were conducted using the Pregnancy Anxiety Questionnaire-Revised-2 (PRAQ-R2). Results Most participants (63%) were 25-35 years old. The majority (85.6%) were Bahraini nationals, and 52.2% were university-educated. Almost two-thirds were unemployed, 28.1% had associated chronic comorbidities, 3.1% had associated psychiatric disorders, 15% had a high level of anxiety, and 38% had a moderate level of anxiety. Employed participants had a significantly higher level of anxiety (p=0.022) than housewives/unemployed participants. Participants' levels of anxiety differed significantly according to their gestational age (p=0.043), with the highest anxiety among those in their third trimester (15.7%). Participants' anxiety levels were significantly higher among those with previously complicated pregnancies (p=0.002). Moreover, those with unplanned current pregnancy had significantly higher anxiety levels (p=0.019). Conclusions This study showed that anxiety seems to be a common disorder among pregnant women in Bahrain. It was more prevalent during the third trimester, and its occurrence was associated with the pregnant woman's employment, the occurrence of previously complicated pregnancies, and unplanned current pregnancies.

Understanding the impact of formulation design on microstructure and drug release from porous microparticle-based tretinoin topical gels.

For proportionally formulated intermediate strengths of a topical product, the relationship of drug release across multiple strengths of a given product is not always well understood. The current study aims to assess the proportionality of tretinoin release rates across multiple strengths of tretinoin topical gels when manufactured using two different methods to understand the impact of formulation design on drug product microstructure and tretinoin release rate. Two groups of tretinoin gels of 0.04 %, 0.06 %, 0.08 % and 0.1 % strengths were manufactured. Gels in Group I were prepared by incorporating 4-10 % g/g of 1 % w/w tretinoin-loaded microparticles into a gel base. Gels in Group II were manufactured using 10 % g/g of the microparticles that were loaded with increasing amounts (0.4-1 % w/w) of tretinoin. The two groups of gels were characterized by evaluating microstructure using a polarized microscope, rheology using an oscillatory rheometer, and drug release using Vison® Microette™ Hanson vertical diffusion cells. The microscopic images were used to discriminate between the two groups of gels based on the abundance of microparticles in the gel matrix observed in the images. This abundance increased across gels of Group I and was similar across gels of Group II. The rheology parameters, namely viscosity at a shear rate of 10 s-1, shear thinning rate, storage, and loss modulus, increased across gels of Group I, and were not significantly different across gels of Group II. The release rate of tretinoin from the drug products was proportional to the nominal strength of the drug product in both Group I and Group II, with a correlation coefficient of 0.95 in each case, although the absolute release rates differed. Overall, changing the formulation design of tretinoin topical gels containing porous microparticles may change the physicochemical and structural properties, as well as the drug release rate of the product. Further, keeping the formulation design consistent across all strengths of microparticle-based topical gels is important to achieve proportional release rates across multiple strengths of a given drug product.

Trends in women's height and the effect of early childbearing on height retardation: An analysis of the height of Bangladeshi women born between 1974 and 1998.

Background: Depending on race, ethnicity, and region, genetic variants determine human height by 65% to 80%, while the remaining variance of 20% to 35% is influenced by nutrition and other individual or environmental exposures in the early years of life. An improvement in nutrition and health in the early years in a population underprivileged in health and nutrition will likely increase the group's average height. Due to outstanding improvements in these areas in recent decades, we hypothesised that the average height of Bangladeshi women has increased. Moreover, because pregnancy at an early age affects women's health and nutrition, we hypothesised that women who began childbearing early would experience growth retardation compared to women who had pregnancies at a later age. Methods: We used data from five national surveys conducted between 2004 and 2018 that collected height data from ever-married women aged 15-49 years. We analysed the height of women aged 20-29 years (born between 1974 and 1998) and examined the mean height by birth years, age at first birth (AFB), economic status, religion and region. We conducted multiple linear regression models, controlling for the differential effects of the socio-demographic characteristics on women's height over time and by AFB. Results: The average height of women born between 1974 and 1998 significantly increased by 0.03 cm annually, with fluctuations between 150.3 and 151.6 cm. We also found an association between age at childbearing and height in adulthood - women who began childbearing before age 17 were approximately one centimetre shorter in adulthood than those who began childbearing at a later age. Conclusions: We found evidence of an increasing trend in women's height in Bangladesh and an inhibiting effect of early teenage childbearing on attaining the potential growth of women. The findings call for further studies to investigate early childbearing and its consequences on women's and their children's growth in diverse settings, considering socio-cultural customs influencing early marriage and childbearing.

Religious disparities in health in Bangladesh-the case of hypertension and diabetes: evidence from two nationally representative cross-sectional surveys.

OBJECTIVES: Religious affiliation, beliefs, and practices shape lifestyles and disease risks. This study examined Hindu-Muslim differences in the prevalence and management of hypertension and diabetes in Bangladesh, a religiously plural country with 91% Muslims and 8% Hindus. DESIGN, SETTINGS AND PARTICIPANTS: We used the nationally representative 2011 Bangladesh Demographic and Health Survey (BDHS) and 2017-2018 BDHS data. The 2011 BDHS collected blood pressure (BP) data with an 89% response rate (RR) and fasting blood glucose (FBG) data (RR 85%) from household members aged 35 years and above. The 2017-2018 BDHS collected BP and FBG data from household members aged 18 years and above with 89% and 84% RRs, respectively. We analysed 6628 participants for hypertension and 6370 participants for diabetes from the 2011 BDHS, 11 449 for hypertension and 10 744 for diabetes from the 2017-2018 BDHS. METHODS: We followed the WHO guidelines to define hypertension and diabetes. We used descriptive statistics and multiple logistic regression to examine the Hindu-Muslim differences in hypertension and diabetes, and estimated predicted probabilities to examine the changes in hypertension and diabetes risk over time. RESULTS: Nine in 10 of the sample were Muslims. About 31% of Hindus and 24% of Muslims were hypertensive; 10% of both Hindus and Muslims were diabetic in 2017-2018. The odds of being hypertensive were 45% higher among Hindus than Muslims (adjusted OR: 1.45; 95% CI: 1.23 to 1.71; p<0.001). The levels of awareness, medication and control of hypertension were similar between the religious groups. Between the 2011 and 2017-2018 BDHS, the Hindu-Muslim difference in the prevalence of hypertension increased non-significantly, by 3 percentage points. CONCLUSIONS: Further studies on religious-based lifestyles, Hindu-Muslim differences in diet, physical activity, stress, and other risk factors of hypertension and diabetes are needed to understand Hindus' higher likelihood of being hypertensive, in contrast, not diabetic compared with Muslims.

Sickle Cell Trait and Adverse Pregnancy Outcomes: Is There a Link?

Objective The objective is to assess the overall prevalence of maternal and neonatal pregnancy-related complications, and to compare their frequency among women with sickle cell trait (SCT) and those with normal hemoglobin patterns to examine the association between SCT and maternal and neonatal outcomes. Methods A retrospective cross-sectional case-control study was conducted by reviewing medical data from the labor room registry book and electronic database. All pregnant ladies delivered in Salmaneya medical complex from January 1 to December 31, 2019 were included. Patients were divided into two groups based on the presence or absence of SCT. Adverse maternal and neonatal outcomes were compared between the two groups.  Results Out of the 5,067 pregnant women reviewed, 934 (18.4%) were included (460 (49.3%) with SCT and 474 (50.7%) with healthy controls). Overall, maternal, and neonatal complications were noted in 40.8% (n=381) and 16.3% (n=152), respectively. In univariate analysis, patients with SCT were significantly more likely to underwent cesarean sections compared to healthy women, 28.7% (n=132) vs. 21.7% (n=103), respectively (P=0.044) and to have more intrauterine fetal death (3% [n=14] vs. 0.2% [n=1], respectively (P<0.0001). No significant differences were found between the two groups in terms of the occurrence of the pregnancy-related hypertensive disorder, gestational diabetes, small for gestational age, and preterm delivery.  Conclusion The result of this large, retrospective cross-sectional, case-control study shows that pregnant women with SCT were associated with an increase in intrauterine fetal death in comparison with pregnant women with normal hemoglobin. There were no differences found in pregnancy-related hypertensive disorder, gestational diabetes, small for gestational age, and preterm delivery. This result will emphasize the requirement of additional studies to scrutinize these findings and to determine whether there may be a benefit of a unique antenatal surveillance guideline for such patients.

Effects of formulation variables on the in vitro performance of testosterone transdermal gel.

The variation in the critical formulation variables during life-cycle of the drug product may result in undesirable changes in product performance. The current study aimed at evaluating the effects of formulation variables on the in vitro performance of carbopol-loaded testosterone gel. The formulation variables included concentrations of permeation enhancers, testosterone, ethanol, carbopol and sodium hydroxide. In vitro evaluation of the product performance included assessment of the rheological and morphological properties, kinetics of ethanol evaporation, and drug permeation through human cadaver skin. The results revealed that carbopol, sodium hydroxide and testosterone concentrations increased the viscosity of the gels significantly (p < 0.05). However, carbopol concentration was the only critical variable to affect the yield stress of the gel. The concentration of ethanol was critical to metamorphosis of the gel due to solvent evaporation upon application to skin with minor contributions from other formulation variables. The increase in concentration of isopropyl myristate or isopropyl palmitate to 5%, ethanol to 70%, and testosterone to 2%, enhanced the testosterone permeation across the skin by ten-folds. Synergistic effects of ethanol and permeation enhancers on testosterone permeation was observed. In conclusion, strict control over the critical formulation variables should be exercised during manufacturing to ensure desired product performance.

Identification of critical formulation parameters affecting the in vitro release, permeation, and rheological properties of the acyclovir topical cream.

To understand effects of formulation variables on the critical quality attributes (CQA) of acyclovir topical cream, this study investigated effects of propylene glycol (PG), poloxamer, and sodium lauryl sulfate (SLS) concentrations, acyclovir particle size, and formulation pH of the acyclovir cream. Fifteen formulations were prepared and characterized for rheological properties, particle size distribution, drug release and in vitro skin permeation. Drug distribution between various phases of the cream was determined. The concentration of soluble acyclovir in the aqueous phase was determined as a surrogate of the equilibrium with other acyclovir species in the cream. The interaction among effects of the formulation variables on the amount of acyclovir retained by skin was also evaluated. The results showed that PG significantly (p < 0.05) increased the yield stress, viscosity, drug concentration in the aqueous phase, and drug release. The PG and SLS significantly (p < 0.05) increased acyclovir retention by skin samples. Particle size of acyclovir inversely affected the drug release. This study revealed that the employed concentrations of PG and SLS and particle size of the dispersed acyclovir are critical formulation variables that should be carefully controlled when developing acyclovir topical creams with desired performance characteristics.

Application of synthetic membranes in establishing bio-predictive IVPT for testosterone transdermal gel.

The current study investigated the use of synthetic membranes in developing a bio-predictive in vitro permeation testing (IVPT) method for 1.62% testosterone gel. The IVPT studies were carried out using both Franz (FC), and Flow-through (FTC) diffusion cells. The experimental variables included the type of synthetic membranes (hydrophilic polyamide nylon, polysulfone tuffryn and STRAT-M (SM) membrane) and the type of receiver media (phosphate buffer containing various concentrations of sodium lauryl sulfate). In vivo drug release rates were obtained from published reports for 1.62% testosterone gel applied to either abdominal area (treatment group A), upper arms/shoulders (treatment group B), or alternating between abdomen and arms/shoulders (treatment group C). The in vitro-in vivo correlations were established using GastroPlus software. The best IVPT method was selected based on establishing point-to-point correlation with the in vivo data of treatment group A with minimal prediction errors (%PE) of AUC0-24 and Cmax. The results showed that the IVPT method which employed the FTC diffusion system, SM membrane and phosphate buffer without surfactant established the best IVIVR model with a correlation coefficient (R2) of 0.9966 and an exponential function of Y = (1.35)5 × X3.6. The in vivo data obtained from treatment group A and B was used for internal validation of the prediction model. The validation data was acceptable, with %PE of less than 10% for both AUC0-24 and Cmax. In conclusion, these results suggest that bio-predictive IVPT methods for testosterone gels may be developed using synthetic membranes and diffusion apparatus by varying the composition of the receiver medium.

Drug recrystallization in drug-in-adhesive transdermal delivery system: A case study of deteriorating the mechanical and rheological characteristics of testosterone TDS.

This study investigated the effects of drug recrystallization on the in vitro performance of testosterone drug-in-adhesive transdermal delivery system (TDS). Six formulations were prepared with a range of dry drug loading in the adhesive matrix from 1% to 10% w/w with the aim of generating TDS with various levels of drug crystals. We visually quantified the amount of crystals in TDS by polarized light microscopy. The effect of drug recrystallization on adhesion, tackiness, cohesive strength, viscoelasticity, drug release, and drug permeation through human cadaver skin were evaluated for these TDS samples. The Optical images showed no crystals in 1% and 2% testosterone TDSs; however, the amount of crystals increased by increasing testosterone loading from 4 to 10%. A proportional and significant decrease (p < 0.05) in tack, peel, and shear strength of the adhesive matrix with increasing amount of crystals in TDS was observed. The drug crystals resulted in a proportional deterioration of the viscoelastic properties of the adhesive matrix. The 2% testosterone TDS showed faster drug release rate when compared to 1% testosterone TDS. The increase in drug loading from 2% to 4% w/w slightly increased the cumulative amount of testosterone released. Further increase in drug loading in TDS to 6, 8, and 10% was nonsignificant (p > 0.05) to affect the drug release and permeation. In conclusion, this study demonstrated that the extent of drug recrystallization can be quantitatively correlated with the deterioration of performance characteristics of TDS products.

Assessing Drug Release from Manipulated Abuse Deterrent Formulations.

There is a need to develop in vitro dissolution methods that discriminate for particle size of the manipulated abuse deterrent formulation (ADF) and that can be used for in vivo predictive models since dissolution methods developed for intact formulation might not be suitable for manipulated ones. A vertical diffusion cell (VDC) and United States Pharmacopeia (USP) Apparatus 1, 2, and 4 were evaluated for measuring the dissolution of intact and manipulated metoprolol succinate tablets with abuse deterrent-like properties. These tablets were physically manipulated to produce fine (106-500 µm) and coarse (500-1000 µm) powder samples. The VDC method was not able to discriminate the effect of particle size on drug release with varied stirring rate (200 to 800 rpm), molecular weight cut-off (MWCO, 3-5 kDa to 12-14 kDa) of the diffusion membrane, or composition and ionic strength (0.45% and 0.9%) of receiver medium. Standard and modified USP Apparatus 1 and 2 methods were assessed; however, large variations (RSD > 20%) were observed with USP Apparatus 1 for manipulated product dissolution and floating powder samples caused failure of auto-sampling when using standard USP Apparatus 2. For the USP Apparatus 4 dissolution method, packing configuration (1, 3, 8 layers and blend), ionic strength of dissolution medium (0.017, 0.077, and 0.154 M additional NaCl), and flow rate (4, 8, 16 mL/min) were studied to discriminate the effect of particle size on release. The USP Apparatus 4 dissolution method was optimized by using a packaging configuration of 8 layers with 8 mL/min flow rate which exhibited low variability and complete drug release and it could be used for in vivo predictive models. The dissolution method variables can be optimized for a specific product for desirable reproducibility and discriminatory power when using USP Apparatus 4.

NAG-PEGylated multilamellar liposomes for BBB-GLUT transporter targeting.

The primary objective of the research study is to investigate Glucose (GLUT) transporter targeting of the drug (Citalopram-Hbr) for increased permeability across the Blood-Brain Barrier (BBB). The current study reports the development, physicochemical characterization, cytotoxicity analysis and in-vitro BBB permeability assessment of the Citalopram-Hbr liposomal formulations. Rat Primary Brain Microvascular Endothelial Cells (RPBECs) were used for cytotoxicity analysis and drug permeability testing. Five N-Acetyl Glucosamine (NAG) coated PEGylated multilamellar liposomal formulations were prepared and tested. Permeability of the liposomal formulations was evaluated in RPBECs monolayer. The particle size of the formulations ranged from 13 to 4259 nm. Entrapment efficiency was 50-75%. Cytotoxicity analysis indicated viability (>90%) for all five formulations (0.3-1.25 mg/ml). Apparent drug permeability (Papp) of the formulations ranged from 5.01 × 104 to 15 × 104 cm/min. The study demonstrated successful preparation of NAG-coated PEGylated multilamellar liposomal formulations with high drug entrapment efficiency. Cytotoxicity data indicated that the formulations were well tolerated by the cells up to a concentration of 1.25 mg/ml. Transport study data demonstrated that RPBMECs monolayers can be employed as a robust screening tool for future drug transport studies targeting GLUT transporter on the BBB. The drug permeability values provide a promising preliminarily proof that NAG-coated liposomal formulations can be an effective tool for BBB-GLUT transporter targeting.

Effect of Isopropyl Myristate on Transdermal Permeation of Testosterone From Carbopol Gel.

The objective of the present study was to investigate the effect of isopropyl myristate (IPM) on the in vitro permeation of testosterone through human cadaver skin from carbopol gels. Six testosterone gel formulations were prepared using different IPM contents of 0%, 0.4%, 0.7%, 1%, 2%, and 3%. The gels were characterized for drug permeation, matrix morphology, pH, kinetics of ethanol evaporation, and viscosity. Mass balance studies were performed to estimate testosterone distribution among the compartments of diffusion cells. All formulations exhibited pH values of 5.1 and viscosities of 1.25-1.75 Pa.s depending on IPM contents. Under occlusive condition, testosterone flux was found to increase significantly (p < 0.05) by increasing IPM content. Gels containing 2% IPM exhibited 11-fold increase in flux compared with formulation devoid of IPM. Ethanol was found to have a synergistic effect with IPM in enhancing testosterone flux. Mass balance analysis showed that testosterone was in a saturated state in the skin. Conducting permeation experiments under nonocclusive condition was nondiscriminating because of the evaporation of alcohol and consequent precipitation of drugs. Based on demonstrated effect of IPM on product performance, the final IPM concentration should be controlled with minimal variation during manufacturing and shelf life of drug product.

Trends in equity in use of maternal health services in urban and rural Bangladesh.

BACKGROUND: Maternal healthcare utilization is a major determinant of maternal mortality. Bangladesh is experiencing a rapid pace of urbanization with all future growth in population expected to be in urban areas. Health care infrastructure is different in urban and rural areas thus warranting an examination of equity in use rates of maternal healthcare. This paper addresses whether the urban-rural and rich-poor gaps in use of selected maternal healthcare indicators have narrowed or widened over the last decade. The paper also explores changes in the service provider environment in urban and rural domains. METHODS: The 2001 and 2010 Bangladesh Maternal Mortality and Health Care Survey data were used to examine trends in use of antenatal care from medically trained providers and in deliveries taking place at health facilities. Separate wealth quintiles were constructed for urban and rural areas. The concentration index was calculated for urban and rural areas to measure equity in distribution of antenatal care (ANC) and facility deliveries across wealth quintiles in urban and rural domains. RESULTS: The gap in use of ANC provided by medically trained personnel narrowed in urban and rural areas between 2001 and 2010 while that in facility deliveries widened. The difference in use of ANC by the rich and the poor was not as pronounced as that in utilization of facilities for deliveries. Over the last decade, equity in utilization of health facilities for deliveries has improved at a faster rate in urban areas. Private sector has surpassed the public sector and appears to be the dominant provider of maternal healthcare in both domains with the share of NGOs increasing in urban areas. CONCLUSIONS: The faster pace of improvement in equity in maternal healthcare utilization in urban areas is reflective of the changing service environment in urban and rural areas, among other factors.

Microdroplet digital PCR: detection and quantitation of biomarkers in archived tissue and serial plasma samples in patients with lung cancer.

INTRODUCTION: There is much interest in the use of noninvasive biomarkers in the management of lung cancer, particularly with respect to early diagnosis and monitoring the response to intervention. Cell-free tumor DNA in patients with cancer has been shown to hold potential as a noninvasive biomarker, in which the response to treatment may be evaluated using a blood test only. Multiple technologies have been suggested as being appropriate to measure cell-free tumor DNA. Microdroplet digital polymerase chain reaction (mdPCR) has a number of attributes that suggest it may be a useful tool for detecting clinically relevant genetic events. It offers precise and accurate quantitation of mutant alleles, including rare variants. METHODS: We evaluate the performance of mdPCR in the analysis of DNA extracted from reference standards, tumor biopsies, and patient plasma. RESULTS: The potential of mdPCR to detect clinically relevant mutations is demonstrated, in both formalin-fixed paraffin-embedded material and plasma. Furthermore, we show that mdPCR can be used to track changes in peripheral blood biomarkers in response to treatment and to detect the emergence of drug-resistant clones. CONCLUSIONS: MdPCR has potential as a tool to detect and quantify tumor-derived mutational events in cell-free DNA from patients with lung cancer.

QbD approach to investigate product and process variabilities for brain targeting liposomes.

Efficacy of central nervous system-acting medications is limited by its localization and ability to cross the blood-brain barrier (BBB); therefore, the crux is in designing delivery systems targeted to cross the BBB. Toward this objective, this study proposed pegylated and glycosylated citalopram hydrobromide (Cit-HBr) liposomes as a delivery approach for brain targeting. The multicomponent liposomes were evaluated for drug encapsulation, vesicular size, size distribution, conductivity and drug release characteristics. Moreover, the interaction among the employed components was evaluated by Fourier transform infrared, differential scanning calorimetric and X-ray diffraction analysis. Through a systematic screening design of formulation and process variables in the optimization phase, an improvement of Cit-HBr loading, fine vesicular size with narrow size distribution, greater stability and sustained release features were achieved. The compatibility studies unveiled a significant interaction between Cit-HBr and dicetyl phosphate to control drug encapsulation and release properties. The optimization process showed a minimal range of design space to achieve the preset desirability; more precisely dicetyl phosphate, polyethylene glycol, N-acetyl glucosamine and freeze-thaw cycles of 3%, 5%, 4% and 2 cycles, respectively, were used. Using brain endothelial cell models, the optimized formulations showed an acceptable cell viability with preserved monolayer integrity and an enhanced flux and permeability. Thus, this study has proposed an optimized pegylated and glycosylated vector that is a promising step for brain targeting.

Population and family planning in Bangladesh.

INTRODUCTION: The family planning programme (FPP) in Bangladesh and its role in reducing the fertility rate in the country has been at the centre of much scholarly debate. The current contraceptive prevalence rate (CPR) is 61%- double the rate observed in Pakistan, while the total fertility rate is 2.3 children per woman. This paper highlights both the supply-and demand-side factors explaining trends in contraceptive use over the last four decades. It identifies the challenges plaguing the programme today that range from funding and staffing deficiencies to bottlenecks in procurement processes. METHODOLOGY: The paper uses secondary data sources such as Bangladesh Demographic and Health Survey (BDHS) 2004 and 2011 to show Family Planning trends in Bangladesh and uses the Spectrum software to forecast trends for the year 2015. RESULTS: The central message is that the current contraceptive method mix, which is heavily biased towards temporary methods, cannot support a sustained decline in fertility. The authors' projected estimates reveal that in order to achieve replacement-level fertility by 2016, users of long-acting and permanent methods would need to be increased by 8-9 million. Drawing on global experiences, the paper outlines greater flexibility in the use of funds and a regionally-targeted approach, among other options, that could be adopted to ensure that national population targets are met.

Efficacy of fine-needle aspiration biopsy in diagnosis of breast cancer: a retrospective study of 303 cases in Bahrain.

Breast cancer is a leading cause of death in many countries worldwide and breast lesions remain a common diagnostic dilemma. Fine-needle aspiration biopsy (FNAB) has been suggested as the most important, first line, minimally invasive measure in the management of patients with breast lesions. The aim of this study is to evaluate the efficacy of FNAB in patients with breast lesions by comparing the diagnostic accuracy of cytology results with that of the definitive histological examination outcome and also to investigate the added value of a single aspirator experience to the overall diagnostic precision and compared with the internationally published results. A retrospective study of 303 breast FNAB samples were carried out by a single experienced cytopathologist with complete comparison records.The prevalence of positive cytologic diagnosis for the breast cancer was determined to be 20.4%. The overall diagnostic accuracy of FNAB was 97.9%, with a specificity and sensitivity of 98.3 and 96.5%, respectively. The overall positive and negative predictive values were determined to be 93.2 and 99.2%, respectively. In addition, the sensitivity was comparable in cases that have been attempted by palpation-guided sampling compared with those aspirations that were carried out under US guidance.Results from this study confirm that FNAB biopsies performed and reported by a dedicated, single, skilled cytopathologist are highly effective in diagnosis of breast lesions and reliable in differentiating benign and malignant breast lesions with an overall high efficacy in a specialized laboratory-based FNAB clinic.

Deletion of a previously uncharacterized flagellar-hook-length control gene fliK modulates the sigma54-dependent regulon in Campylobacter jejuni.

A previously unannotated, putative fliK gene was identified in the Campylobacter jejuni genome based on sequence analysis; deletion mutants in this gene had a 'polyhook' phenotype characteristic of fliK mutants in other genera. The mutants greatly overexpressed the sigma(54)-dependent flagellar hook protein FlgE, to form unusual filamentous structures resembling straight flagella in addition to polyhooks. The genome sequence reveals only one gene predicted to encode an orthologue of the NtrC-family activator required for sigma(54)-dependent transcription. Hence, all sigma(54)-dependent genes in the genome would be overexpressed in the fliK mutant together with flgE. Microarray analysis of genome-wide transcription in the mutant showed increased transcription of a subset of genes, often downstream of sigma(54)-dependent promoters identified by a quality-predictive algorithm applied to the whole genome. Assessment of genome-wide transcription in deletion mutants in rpoN, encoding sigma(54), and in the sigma(54)-activator gene flgR, showed reciprocally reduced transcription of genes that were overexpressed in the fliK mutant. The fliA (sigma(28))-dependent regulon was also analysed. Together the data clearly define the roles of the alternative sigma factors RpoN and FliA in flagellar biogenesis in C. jejuni, and identify additional putative members of their respective regulons.