The roles of four conserved basic amino acids in the reaction catalyzed by the ferredoxin-dependent nitrate reductase from the cyanobacterium Synechococcus sp. PCC 7942 have been investigated using site-directed mutagenesis in combination with measurements of steady-state kinetics, substrate-binding affinities and spectroscopic properties of the enzyme’s two prosthetic groups. Replacement of either Lys58 or Arg70 by glutamine leads to a complete loss of activity, with both the physiological electron donor, reduced ferredoxin and with a non-physiological electron donor, reduced methyl viologen. More conservative, charge-maintaining K58R and R70K variants were also completely inactive. Replacement of Lys130 by glutamine produced a variant that retained 26% of the wild-type activity with methyl viologen as the electron donor and 22% of the wild-type activity with ferredoxin as the electron donor, while replacement by arginine produces a variant that retains a significantly higher percentage of the wild-type activity with both electron donors. In contrast, replacement of Arg146 by glutamine had minimal effect on the activity of the enzyme. These results, along with substrate-binding and spectroscopic measurements, are discussed in terms of an in silico structural model for the enzyme.
The present paper discusses the effect of manganese doping on the structural stability and electronic band gap of chiral (2, 1), armchair (3, 3), and zigzag ((6, 0) and (10, 0)) single walled GaN nanotube by using density functional theory based Atomistix Toolkit (ATK) Virtual NanoLab (VNL). The structural stability has been analyzed in terms of minimum ground state total energy, binding, and formation energy. As an effect of Mn doping (1–4 atoms), all the GaN nanotubes taken into consideration show semiconducting to metallic transition first and after certain level of Mn doping changes its trend.
This prospective cohort study was conducted to find the role of tumor neovascularization in skin melanoma measured by preoperative Doppler ultrasound flowmetry in determining the 15-year outcome. Setting: Department of Surgery, University of Wales College of Medicine, Cardiff, UK. Seventy-one primary melanomas in 67 patients were studied with a 10 MHz Doppler ultrasound flowmeter. The flow signals were recorded on an audiotape. The peak systolic frequency, mean systolic frequency, and minimum diastolic frequency were measured on a spectrum analyzer. The follow-up (median 144 months) information is complete till December 2005 on 63 patients. Blood flow signals were detected in 41 lesions; these were labeled Doppler flow positive. No flow was detected in 22 lesions, labeled Doppler flow negative. Among the Doppler flow positive group, 39% patients have died with metastatic melanoma, whereas none of the patients with a Doppler-negative lesion have died or developed any recurrence. Higher peak systolic frequency (above 2,500 MHz.) was associated with a hazard ratio for death due to melanoma of (HAZARD RATE = 5.99). Higher risk of death, locoregional, and systemic recurrences were associated with higher peak systolic frequency. Doppler flowmetry performed preoperatively is a noninvasive, quick, and simple method to assess tumor blood flow which may help in predicting long-term survival and planning neoadjuvant therapies aimed at inhibiting angiogenesis or targeting tumor vasculature.
Tumor blood flow; Neovascularization; Malignant melanoma; Recurrence; Doppler ultrasound flowmetry; Cohort study; Survival
Role of (18 [F] fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose [FDG] positron emission tomography-computed tomography [PET-CT]) in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer and compare results with sentinel lymph node biopsy (SLNB).
A total of 37 patients of proven T1T2N0 breast cancer were included in the study. Patients with past history of breast surgery, T3T4 disease, uncontrolled diabetes mellitus and pregnant patients were excluded from the study. Pre-operative FDG PET-CT was performed followed by sentinel lymph node (SLN) biopsy with blue dye or combined technique.
SLN was identified in 32 of 37 patients with an identification rate of 86.48% (32/37). With combined technique SLN identification rate was 100% (6/6) while with blue dye alone; it was 83.8% (26/31). Among 37 patients, 16 had axillary metastases of which 12 had macrometastases and four had micrometastases detected by immunohistochemistry (IHC). Of 12 patients with axillary macrometastases, skip metastases were present in two patients in whom SLN was negative and in two patients SLN was not identified, but axillary dissection showed metastases. PET-CT had shown sensitivity, specificity, negative predictive value and positive predictive value of 56%, 90%, 73%, and 81.8%, respectively. IHC of SLN detected four patients with micrometastases upstaging the disease by 11% (4/37).
Because FDG PET-CT has a high specificity in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer patients according to the results of this study if FDG PET-CT is positive in axillary lymph nodes, axillary lymph node dissection may be considered instead of SLNB.
Breast cancer; fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography; immunohistochemistry; sentinel lymph node biopsy
Perturbations in cell adhesion molecules are linked to alterations in cadherin-catenin complexes and likely play major roles in invasion and metastasis; their impact on early precancerous stages remains yet unknown. We showed ALCAM overexpression in early oral lesions and its cytoplasmic accumulation in oral squamous cell carcinoma (OSCC) to be a predictor of disease progression and poor prognosis. This study tested the hypothesis that alterations in E-cadherin and β -catenin expressions are early events in oral tumorigenesis, associated with disease prognosis, and correlate with perturbations in ALCAM expression.
Expressions of E-cadherin and β-catenin were analyzed in the same cohort of 105 OSCCs, 76 oral lesions and 30 normal oral tissues by immunohistochemistry and correlated with clinicopathological parameters and prognosis. The effect of siRNA mediated ALCAM knockdown on E-cadherin and β -catenin was determined using western blot, confocal microscopy and RT-PCR analysis in oral cancer cells.
Significant loss of membranous E-cadherin and β-catenin expression was observed from normal, hyperplasia, dysplasia to OSCCs (ptrend <0.001); and correlated with cytoplasmic ALCAM accumulation in OSCCs (p = 0.006). Multivariate analysis revealed β-catenin membrane loss and ALCAM/β-cateninnuclear/cytoplasmic accumulation to be significant predictors for late clinical stage (p<0.001, OR = 8.7; p = 0.006, OR = 9.9, respectively) and nodal metastasis (p = 0.003, OR = 3.8; p = 0.025, OR = 3.4 respectively). Cox’s regression showed E-cadherin membrane loss/ALCAM cytoplasmic expression [p<0.001; HR = 4.8] to be independent adverse prognosticators in OSCCs. siRNA mediated silencing of ALCAM resulted in concurrent increase in E-cadherin and β-catenin both at the transcript and protein levels.
Losses of E-cadherin and β-catenin expressions are early events in oral tumorigenesis; their associations with aggressive tumor behavior and disease recurrence underscore their potential as prognostic markers. Correlation of loss of E-cadherin and β-catenin with cytoplasmic ALCAM accumulation both in vitro and in in vivo suggests that these dynamic changes in cell adhesion system may play pivotal role in oral cancer.
In the present article, we discuss that why most breast cancer screening trials have a flawed origin. We suggest some solutions to correct these flaws so that more valid and reliable screening trials can be conducted in the future.
Breast cancer; Screening trials; Bias; Quality of life; Mammography
Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor growth. Moreover, poorly oxygenated central tumor area remains relatively radio or chemo resistant. HBO therapy is known to elevate the levels of dissolved oxygen and eliminates tumor hypoxia. It has been one of the modalities in cancer treatment; therefore its optimization is important. In this experimental study, no cancer enhancing effect was seen during the course of HBO therapy; however, post therapy there was an accelerated growth and progression of tumor. HBO treated mice lived shorter and the response to therapy was dose & tumor volume dependent. HBO therapy probably exert its effect on the cancer proliferating cells through multiple pathways such as increased DNA damage, apoptosis & geno-toxicity leading to slow cancer progression while post therapy tumorigenic effect could be due to impaired DNA repair mechanism, mutagenic effect & aneuploidy as well as altered blood supply & nutrients. Tumor growth reached plateau with time and this finding validated theoretical model predicting tumor reaching an asymptotic limit. While, marked asymmetry observed in tumor volume progression or cancer cell proliferation rate in each of the experimental C3H mouse suggested a need for an alternate small animal pre-clinical cancer therapeutic model.
Myofibroblastomas are soft-tissue neoplasms that are thought to arise from myofibroblasts. They are mostly observed in males 41–85 years of age; however, this lesion also occurs in women. The usual clinical presentation is a unilateral painless lump that is not adherent to overlying or underlying structures. Microscopically, myofibroblastomas can be divided into 5 subtypes: classical, epithelioid, collagenised, cellular, and infiltrative. Mammary ducts and lobules are absent in the typical histological subtypes and the adjacent breast parenchyma may form a pseudocapsule. The majority of myofibroblastomas are immunoreactive for CD34, desmin, smooth muscle actin, and vimentin and are negative for cytokeratin and S-100 protein. We present a case of a giant myofibroblastoma arising in the background of gynecomastia in an adult male.
breast; gynecomastia; mesenchymal; myofibroblastoma; spindle cell
We conducted a randomized trial to evaluate effectiveness of Centchroman in control of mastalgia and compared it with Danazol. Research Question- Is proportion of pain relief achieved by Centchroman similar to or inferior to that achieved by Danazol? In a randomized controlled trial of Centchroman vs. Danazol in mastalgia, 81 patients with mastalgia were studied. Thirty-nine patients were randomized to Danazol arm and 42 in Centchroman arm. The treatment was given for 12 weeks, followed by observation for 12 weeks. The pain was measured by visual analogue scale (VAS) of 0–10. At 12 weeks 89.7% women achieved reduction in pain score to ≤3 in Centchroman group (pvalue 0.001). In Danazol group 69.44% women achieved reduction in pain score to ≤ 3 (p = 0.001). Three months after stopping therapy, Centchroman was more effective in pain score reduction at 24 weeks as compared to Danazol (p = 0.019). Centchroman is an effective, safe and inexpensive alternative to Danazol for treatment of mastalgia.
Electronic supplementary material
The online version of this article (doi:10.1007/s12262-010-0216-z) contains supplementary material, which is available to authorized users.
Centchroman; Danazol; Randomized trial; Mastalgia; Breast pain; Antiestrogen; Non-inferiority trial
Breastfeeding is one of the most important determinants of child survival, birth spacing, and the prevention of childhood infections. The beneficial effects of breastfeeding depend on its initiation, duration, and the age at which the breastfed child is weaned. Breastfeeding practices vary among different regions and communities.
To assess the pattern of infant feeding and its relation to certain practices of maternity and newborn care, and to assess the knowledge of mothers on the advantages of exclusive breastfeeding.
Materials and Methods:
The cross-sectional study was carried out in randomly selected villages of the Bhojipura Block of Bareilly district, Uttar Pradesh. A total of 123 women who had delivered within the last year were interviewed in a house-to-house survey. A study instrument was used to collect data. Chi- square test and regression analysis were used to analyze the data.
Most of the mothers were aged less than 30 years (78.04%) and were Hindus (73.9%). Most were illiterate (69.9%) and belonged to the lower socioeconomic class (97.5%). The majority were housewives (99.1%) and multiparous (68.2%). Most had initiated breastfeeding (78.8%) within 24 hours of delivery. About 15.4% of the infants did not receive colostrum and 22.8% of the infants were not exclusively breastfed. Ghutti (water mixed with honey and herbs), boiled water, tea, and animal milk were commonly used pre-lacteal feeds. About 47.2% of the respondents were not aware of the benefits of exclusive breastfeeding. About one quarter of the mothers started complementary feeding before the child was six months old. About half the deliveries had taken place at home and only a quarter of the females had had three or more antenatal visits during pregnancy. The birth weight of the majority (78%) of newborns was not measured. A majority (69.9%) of the mothers did not receive advice on child feeding. Multivariate logistic regression analysis showed that maternity and newborn care variables had no significant association with exclusive breastfeeding.
Despite higher rates of early initiation of breastfeeding and exclusive breastfeeding, awareness of the benefits of exclusive breastfeeding was low. This indicates the need to promote awareness of the correct method of infant feeding and care of the newborn. Creating an awareness of the advantages of exclusive breastfeeding will further strengthen and support this common practice in rural communities and avoid an early introduction to complementary foods for sociocultural reasons.
Birth weight; infant feeding practices; rural India
One of the greatest problems for India is undernutrition among children. The country is still struggling with this problem. Malnutrition, the condition resulting from faulty nutrition, weakens the immune system and causes significant growth and cognitive delay. Growth assessment is the measurement that best defines the health and nutritional status of children, while also providing an indirect measurement of well-being for the entire population.
A cross-sectional study, in which we explored nutritional status in school-age slum children and analyze factors associated with malnutrition with the help of a pre-designed and pre-tested questionnaire, anthropometric measurements and clinical examination from December 2010 to April 2011 in urban slums of Bareilly, Uttar-Pradesh (UP), India.
The mean height and weight of boys and girls in the study group was lower than the CDC 2000 (Centers for Disease Control and Prevention) standards in all age groups. Regarding nutritional status, prevalence of stunting and underweight was highest in age group 11 yrs to 13 yrs whereas prevalence of wasting was highest in age group 5 yrs to 7 yrs. Except refractive errors all illnesses are more common among girls, but this gender difference is statistically significant only for anemia and rickets. The risk of malnutrition was significantly higher among children living in joint families, children whose mother's education was [less than or equal to] 6th standard and children with working mothers.
Most of the school-age slum children in our study had a poor nutritional status. Interventions such as skills-based nutrition education, fortification of food items, effective infection control, training of public healthcare workers and delivery of integrated programs are recommended.
Growth monitoring; Malnutrition; School-age Children; Stunting; Wasting
In this sequel, to an earlier article, we discuss the laws of Mechanics, Thermodynamics and Vectors as they apply to soft and bony tissues. These include the Laplace’s Law as applied to colonic perforation, compression therapy, parturition, variceal rupture, disc herniations etc. The Pascal’s Law finds use in hernia repair and the Heimlich maneuver. Trigonometrically derived components of forces, acting after suturing, show ways to reduce cut-through; the thickness and the bite of suture determines the extent of tissue reaction. The heating effect of current explains the optimum gap between the prongs of a bipolar cautery and the use of law of transfer of heat in determining relation between healthy wound healing and ambient temperature.
Mechanics; Laplace; Pascal; Vectors; Suturing; Thermodynamics; Newton; Cautery
Deep vein thrombosis [DVT] is one of the most dreaded complications in post-operative patients as it is associated with considerable morbidity and mortality. Majority of patients with postoperative DVT are asymptomatic. The pulmonary embolism, which is seen in 10% of the cases with proximal DVT, may be fatal. Therefore it becomes imperative to prevent DVT rather than to diagnose and treat. Only one randomized trial has been reported from India to assess the effectiveness of low molecular weight heparin in preventing post-operative DVT. To assess the risk of DVT in North Indian patients following major abdominal operations and to evaluate the effectiveness of Nadroparin, A Low Molecular Weight Heparin (LMWH) therapy in preventing post-operative DVT. Sixty five patients were randomised preoperatively into Group-I; Nadroparin prophylaxis and Group-II: No prophylaxis. The primary outcome was the occurrence of DVT, diagnosed by bilateral lower limb venogram performed, seven to ten days after operation. Secondary outcome measures included adverse effects of radio-opaque dye, intra-operative blood loss, operating time, postoperative platelet count, intraoperative blood transfusion requirements and the total duration of postoperative bed rest. No case of DVT occurred in either group. There was no statistical difference in the risk of secondary outcome measures in the two groups. DVT was not observed in any of the patients, even with several high risk factors indicating a possible protective mechanism in the North Indian population.
Deep vein thrombosis; Post-operative DVT; Low molecular weight heparin; Nadroparin; Venography
The axillary lymph node status is the most important determinant of prognosis in patients with breast cancer. Sentinel lymph node (SLN) biopsy is a safe alternative for axillary clearance with an equal efficacy limiting the morbidity caused by axillary clearance.
Patient and methods
From May 1996 till September 2009, 523 clinically node negative, early breast cancer patients attending our clinic at All India Institute of Medical Sciences were included in the study. They underwent sentinel lymph node biopsy by either combined technique or blue dye alone. All patients irrespective of the axillary status underwent axillary lymph node dissection (ALND).
Of 523 patients, 267 underwent combined technique of sentinel node mapping and 256 underwent blue dye technique alone. The identification rate of sentinel lymph node was 94.3% (253/267) for combined technique and 87.8% (225/256) for blue dye alone. Of 523 patients SLN was identified in 478 patients. The identification rate was 91.3%. The sensitivity = 91.5% (141/154), false negative = 8.4% (13/154), negative predictive value = 96.14% (324/337), and accuracy being 97.2% (465/478).
Sentinel node mapping is a simple and safe technique of identifying the axillary node involvement. Sentinel lymph node biopsy is associated with less arm oedema and shoulder morbidity compared to ALND. However, the results of long term effects of sentinel node approach on tumor recurrence or patient survival are awaited.
Sentinel lymph node biopsy; Axillary lymph node dissection; Axillary node sampling; Lymphatic mapping; Early breast cancer; Immuohistochemistry
In the field of medicine and surgery many principles of physics find numerous applications. In this article we have summarized some prominent applications of the laws of fluid mechanics and hydrodynamics in surgery. Poiseuille’s law sets the limits of isovolaemic haemodilution, enumerates limiting factors during fluid resuscitation and is a guiding principle in surgery for vascular stenoses. The equation of continuity finds use in non-invasive measurement of blood flow. Bernoulli’s theorem explains the formation of post-stenotic dilatation. Reynolds number explains the origin of murmurs, haemolysis and airflow disturbances. Various forms of oxygen therapy are a direct application of the gas laws. Doppler effect is used in ultrasonography to find the direction and velocity of blood flow. In this first part of a series of articles we describe some applications of the laws of hydrodynamics governing the flow of blood and other body fluids.
Hydrodynamics; Poiseuille’s; Equation of continuity; Bernoulli’s; Reynolds number; Doppler effect
We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure.
Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems.
Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels.
Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.
It is a well-known fact that the assessment of the dental development can be related to an individual’s age, but after the age of 21 years when the wisdom teeth also complete their development, there arises a need for an optimal age estimation procedure. With advancing age, there is a reduction in the size of the pulp due to secondary dentin deposition and a measurement of this reduction can also be used as a parameter to assess the age of the individuals, both in the living and dead.
Aims and Objectives:
The purpose of the present study was to evaluate the feasibility of this approach in the estimation of age of adults, using Kvaal’s method in the set sample.
Materials and Methods:
The material consisted of the digital long-cone intraoral periapical radiographs from 50 subjects of either sex in the age group of 15–60 years, who were selected after evaluation for the set inclusion and exclusion criteria. The pulp width and length from radiographs of 6 selected teeth, namely, maxillary central incisor, lateral incisor, and second premolar and mandibular lateral incisor, canine, and first premolar of either right or left side were measured using the RVG trophy software [Trophy® Windows is a software program supplied by Trophy Radiologie (Trophy Windows Version 5.03, Copyright 1993-2002,Trophy RVG patented by Trophy, Chicago)]. In order to compensate for the differences in magnification and angulation, various ratios were calculated and the mean of all ratios (M) was taken as the first predictor, while the difference between the mean of 2 width ratios and the mean of 2 length ratios (W – L) was taken as the second predictor. Different regression formulae for all 6 teeth, 3 maxillary teeth, 3 mandibular teeth, and each of the individual teeth were derived and the age was assessed. The assessed age was then co-related with the actual age of the patient using the Student’s t test.
The results showed that the coefficient of determination (R2) was the strongest (0.198) for the mandibular first premolar indicating that age can be estimated better with this particular tooth. No significant difference was observed between the estimated age and the actual age for all (P>0.05) except in mandibular lateral incisor and maxillary lateral incisor, where a significant difference was observed.
To conclude, the results of the present study suggest the feasibility of Kvaal’s method for age estimation in the set sample
Age estimation; Kvaal’s method; RVG
There are several case reports documenting opportunistic fungal infection in the female genital tract, withr Aspergillus spp being a rarely reported causative organism. We hereby report a case of Aspergillus infection in a 48 year-old, postmenopausal female with carcinoma of the cervix. She presented with features of pelvic inflammatory disease, and an initial routine cervico-vaginal smear revealed severe inflammation along with fungal bodies. The features were consistent with the presence of Aspergillus spp, while the background epithelial cells were negative for intraepithelial malignancy. She was offered therapy for pelvic inflammatory disease. A repeat Papanicolaou smear after two weeks was negative for intraepithelial organisms, but showed the evidence of a high-grade squamous intraepithelial lesion, with biopsy confirming squamous cell carcinoma.
Aspergillus; cervix; papanicolaou smear
Gallstone ileus is a mechanical obstruction caused by the impaction of one or more gallstones within the lumen of any part of the gastrointestinal tract. Although the disorder is a rare cause of small bowel obstruction (1% to 2%), it has been reported to cause up to 25% of cases of non-strangulated small bowel obstruction in patients over 65 years of age.
We report a case of a 67-year-old woman who presented with gallstone ileus following endoscopic retrograde cholangiopancreatography and sphincterotomy for choledocholithiasis. She had a history of terminal ileum resection with ileocolic anastomosis for Crohn's disease. A 3 cm gallstone was found to be impacted just proximal to the previous ileocolic anastomosis. A second gallstone was found on digital examination of the proximal small bowel.
A gallstone may enter the gastrointestinal tract following endoscopic retrograde cholangiopancreatography and sphincterotomy and impact proximal to an anastomotic stricture as demonstrated here. The radiographic image of small bowel obstruction plus air in the biliary tree is a classic diagnostic finding. After stone extraction, the entire small bowel and colon should be digitally examined for further stones.