An appraisal of vascular endothelial growth factor (VEGF): the dynamic molecule of wound healing and its current clinical applications.

Angiogenesis is a critical step of wound healing, and its failure leads to chronic wounds. The idea of restoring blood flow to the damaged tissues by promoting neo-angiogenesis is lucrative and has been researched extensively. Vascular endothelial growth factor (VEGF), a key dynamic molecule of angiogenesis has been investigated for its functions. In this review, we aim to appraise its biology, the comprehensive role of this dynamic molecule in the wound healing process, and how this knowledge has been translated in clinical application in various types of wounds. Although, most laboratory research on the use of VEGF is promising, its clinical applications have not met great expectations. We discuss various lacunae that might exist in making its clinical application unsuccessful for commercial use, and provide insight to the foundation for future research.

Unravelling of the comparative Transcriptomic Profile of Gallbladder Cancer using mRNA sequencing.

BACKGROUND: Gallbladder cancer (GBC) represents a wide geographical diversity as well as heterogeneity in clinical and genomic landscape. There seems to be little progress in the development of diagnostic biomarkers, targeted therapies or individualized approaches to GBC management. In this study, we investigated the whole transcriptome profile of GBC patients using RNA sequencing and identified key genes and pathways associated with gallbladder cancer using bioinformatics. METHODOLOGY: A total of 10 cases of GBC were collected and sequenced. The raw reads of the gallbladder sample was compared with the gallbladder normal control (SRA Database ID: ERX288537: HPA RNA-seq normal tissues gallbladder). Using Gene ontology analysis the differentially expressed genes were categorized into the biological pathway, cellular component, and molecular function. Pathway enrichment analyses, protein-protein interaction, transcription factor and miRNA interaction that regulate the expression of hub genes were conducted using bioinformatics tool. RESULTS: A total of 954 differentially expressed mRNA transcripts were identified, including overexpression of REG4, TMEM238, S100A2, LYPD2, and KRT17, as well as underexpressed genes like CCKAR, IGSF10, CHRM2, CRISP3, and FGF19. Enrichment analysis showed the metabolic pathways to be the top five cancer pathways in gallbladder carcinogenesis besides PI3k-Akt signalling pathway, cAMP signalling pathway, miRNAs in cancer, and cell adhesion profile of GBC. CONCLUSIONS: CCKAR, CDKN2A and LRRK2 were found to be most involved genes in its progression and development through different regulatory pathways. Further, most of the genes were significantly involved in PI3k-Akt, Wnt and hedgehog signaling pathways which have a key role in gallbladder cancer development.

Prevalence of SARS-CoV-2 infection in India: Findings from the national serosurvey, May-June 2020.

BACKGROUND & OBJECTIVES: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. METHODS: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. RESULTS: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. INTERPRETATION & CONCLUSIONS: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

Comparative Analysis of Mutational Profile of Sonic hedgehog Gene in Gallbladder Cancer.

BACKGROUND: Gallbladder cancer has high incidence in northeastern India; mortality too is high as the disease is often diagnosed late. Numerous studies have shown the role of sonic hedgehog (shh) in different cancers, an important ligand of the hedgehog signaling pathway. AIM: This study was carried out to evaluate the shh gene mutations in gallbladder cancer patients. METHODS: PCR-SSCP was performed for shh gene in 50 samples each of gallbladder cancer, cholelithiasis, and control. The samples showing aberration in banding pattern were sequenced. RESULTS: Variation in banding pattern was observed in 20% gallbladder cancer cases, 10% in cholelithiasis, and none of the control (χ 2 = 11.111; p < 0.05). Sequencing results revealed seven novel point mutations in GBC cases. These novel mutations were found to be associated with histopathology (p < 0.05) and stage (p < 0.05) of gallbladder cancer. CONCLUSION: This study reveals several novel individual and repetitive mutations of shh gene in GBC and cholelithiasis samples that may be used as diagnostic markers for gallbladder carcinogenesis.

Locally Advanced Rectal Cancer: What We Learned in the Last Two Decades and the Future Perspectives.

The advancement in surgical techniques, optimization of systemic chemoradiotherapy, and development of refined diagnostic and imaging modalities have brought a phenomenal shift in the treatment of the locally advanced rectal cancer. Although each therapeutic option has shown substantial progress in their field, it is finding their ideal amalgamation which has baffled the clinician and researchers alike. In the effort to identifying the perfect salutary treatment plan, we have even shifted our attention from the trimodal approach to non-operative "watchful waiting" to more recent individualized care. In this article, we acknowledge the scientific progress in the management of locally advanced rectal cancer and compare the opportunities as well as the obstacles while implementing them clinically. We also explore the current challenges and controversies surrounding the multidisciplinary approach and highlight the new trends and recent advances with an ultimate goal to improve the patients' quality of life.

Biofilm and wound healing: from bench to bedside.

The bubbling community of microorganisms, consisting of diverse colonies encased in a self-produced protective matrix and playing an essential role in the persistence of infection and antimicrobial resistance, is often referred to as a biofilm. Although apparently indolent, the biofilm involves not only inanimate surfaces but also living tissue, making it truly ubiquitous. The mechanism of biofilm formation, its growth, and the development of resistance are ever-intriguing subjects and are yet to be completely deciphered. Although an abundance of studies in recent years has focused on the various ways to create potential anti-biofilm and antimicrobial therapeutics, a dearth of a clear standard of clinical practice remains, and therefore, there is essentially a need for translating laboratory research to novel bedside anti-biofilm strategies that can provide a better clinical outcome. Of significance, biofilm is responsible for faulty wound healing and wound chronicity. The experimental studies report the prevalence of biofilm in chronic wounds anywhere between 20 and 100%, which makes it a topic of significant concern in wound healing. The ongoing scientific endeavor to comprehensively understand the mechanism of biofilm interaction with wounds and generate standardized anti-biofilm measures which are reproducible in the clinical setting is the challenge of the hour. In this context of "more needs to be done", we aim to explore various effective and clinically meaningful methods currently available for biofilm management and how these tools can be translated into safe clinical practice.

Wandering Spleen and Acute Gastric Volvulus in an Elderly Woman with Acute Abdomen: A Case Report.

Gastric volvulus is an uncommon clinical condition with the potentially life-threatening complication of acute gastric necrosis. A wandering spleen may also be associated with gastric volvulus and can produce a diagnostic dilemma as the cause of an acute abdomen. We present a case of an elderly woman who presented with acute abdominal symptoms. She did not have the classical Borchardt triad to diagnose gastric volvulus and had a coexisting wandering spleen. Although torsion and ischemia of the wandering spleen were initially thought to be the cause of acute abdomen, a subsequent contrast-enhanced CT (CECT) scan confirmed a coexistent mesenteric-axial gastric volvulus with gangrenous changes. We present this case to highlight a rare combination of pathologies, either of which can confuse the diagnosis or cause a delay in management. Early diagnosis with CECT is emphasized, and segmental resection is feasible when the rest of the viscus can be preserved.

Poor Glycemic Control Is Associated With Lower Interleukin-2 (IL-2) Levels and Low Macrophage Viability in Chronic Diabetic Foot Ulcers (DFUs).

Low macrophage viability in chronic diabetic foot ulcers (DFUs) may lead to inadequate interleukin (IL) expression and the persistence of infection. This study evaluates the association between macrophage function, IL-2 expression, and wound microflora in chronic DFUs. Diabetic patients with DFUs (group 1, n = 40) and without DFUs (group 2, n = 40) were compared for macrophage function in serum by viability testing. Immunological response was measured by serum IL-1ß, IL-2ß, and IL-10 levels. The aerobic and anaerobic microflora of the DFUs were assessed by culture and molecular methods. Demographic, clinical, and biochemical factors were statistically analyzed by χ2 test and Student t test. Multiple correspondence analysis (MCA) was used to detect the pattern of association between glycosylated hemoglobin (hemoglobin A1c), serum IL-2 levels, and macrophage viability. Of the total DFU cases, 22 (55%) showed the presence of polymicrobial microflora. Low macrophage viability with predominant Gram-negative flora was seen in 10 (25%) cases in group 1. Serum IL-2 levels were significantly lower (P = .004) in patients in group 1 along with elevated levels of hemoglobin A1c (P = .038). MCA showed an association between low viability of macrophages and lower IL-2 levels and elevated hemoglobin A1c levels with lower serum IL-2 levels. As compared to group 2, the low viability of macrophages was significantly associated (P = .007) with lower IL-2 levels in group 1. Elevated hemoglobin A1c levels are strongly associated with lower IL-2 levels and low macrophage viability. This might be a contributing factor to the persistence of infections in chronic DFUs.

Wound Healing in the Golden Agers: What We Know and the Possible Way Ahead.

While "population aging" is an accomplishment that deserves acclamation, it is in itself a tremendous challenge. Age-related skin changes, impaired wound healing, and concurrent comorbidities are the deadly triad that contribute most to the development of nonhealing chronic wounds in the elderly. This imposes enormous medical, social, and financial burden. With the rising trend in the aging population, this problem is likely to exacerbate unless multidisciplinary, rapt wound care strategies are developed. The last decade was dedicated to understand the basic biology underlying the wound healing process but most in vitro and animal model studies translated poorly to human conditions. Forthcoming, the focus is on the development of diagnostic and therapeutic strategies to improve healing in this vulnerable age group. Further, understanding the complex pathobiology of cellular senescence and wound healing process is required to develop focused therapy for these "problem wounds" in the elderly.

Significant in-Vitro and in-Vivo Antimicrobial and Antibiofilm Activity of Colloidal Silver Nanoparticles (cAgNPs) in Chronic Diabetic Foot Ulcers.

Infection is a foremost challenge in the cases of wound care, especially in cases of chronic wounds. The present study was conducted to determine the antimicrobial and antibiofilm activity of the colloidal silver nanoparticles (cAgNPs) on Gram positive organisms and to evaluate the in-vivo response of cAgNPs on patients of chronic diabetic foot ulcers (DFUs). cAgNPs were tested against selected Gram-positive organisms like methicillin-sensitive and resistant Staphylococcus aureus (MSSA, MRSA), Enterococcus faecalis and vancomycin resistant enterococci (VRE) using microbroth dilution assay to estimate minimum inhibitory/bactericidal concentration (MIC/MBC). Biofilm inhibition capacity and time kill assay was performed. Further, the in-vivo response of topical application of cAgNPs was evaluated on patients of DFUs. The susceptibility testing demonstrated the MIC and MBC values of the cAgNPs ranging from 0.5µg/ml to 1.0 µg/ml and 1.0 µg/ml to 8 µg/ml against the tested organisms respectively. The cAgNPs showed inhibition of biofilm formation in the low, medium and high biofilm producers by 91%, 83% and 75% respectively at the highest concentration (52ppm). The time kill kinetics showed significant reduction in the number of viable cells (p < 0.0001). Significant reduction in microbial load (p = 0.0062) and in the number of moderate to strong biofilm producing organisms (p = 0.0069) after treatment with cAgNPs was seen. cAgNPs exhibited significant in-vitro bactericidal and bacteriostatic activity against MRSA, MSSA and VRE respectively along with anti-biofilm activity. Additionally, cAgNPs showed significant reduction in microbial load of the chronic DFUs.

Study on Blood Serum Levels of Heavy and Trace Metals in Chronic Non-Healing Wounds.

Wound healing is a complex, highly regulated process that is important in sustaining the skin barrier function. The etiologic relation of specific metals is not adequately described for chronic non-healing wounds. The aim of this study was to estimate heavy and trace metals in chronic non-healing wound and their association with wound healing. The levels of zinc, selenium, copper, magnesium, chromium, cadmium, iron, and lead were estimated in serum of chronic non-healing wound patients using atomic absorption spectrophotometry. The tests were carried out in 50 patients with chronic non-healing wound and thirty healthy volunteers as control. The serum levels of elements namely zinc, selenium, copper, magnesium, and chromium were significantly reduced in chronic non-healing wounds (P < .001) as compared to control. Lead and cadmium levels had shown the significantly increasing trend in chronic non-healing wound cases (P < .001). The present study demonstrated a significant decrease in serum, levels of selenium, zinc, copper, magnesium, iron, and chromium levels in patients with chronic non-healing wound indicating an association between these elements and wound healing. To summarize the findings of our research, hence trace elements were decreasing in chronic non-healing wound patients suggesting their role in wound healing.

Duodenojejunal junction web masquerading as Wilkie's syndrome: report of a case.

Wilkie's syndrome (superior mesenteric artery syndrome) is a rare cause of obstruction to the third part of duodenum due to compression between the superior mesenteric artery and the abdominal aorta. Pathologies like malignant growth in the mesenteric root, the presence of a lymph nodal mass compressing the terminal duodenum, dissecting aortic aneurysm, and intestinal malrotation may mimic the condition, but are not true etiologies of the syndrome. A duodenojejunal web causing narrowing of the duodenojejunal junction and mimicking Wilkie's syndrome has not been described before in the literature. We herein report a case of gastroduodenal obstruction due to a web in the duodenojejunal junction in a young female patient, which closely mimicked Wilkie's syndrome but was finally diagnosed postoperatively. We highlight the first case of its kind in an adult and discuss the challenges in both the diagnosis and management.

Analysis of SET and MYND Domain-Containing Protein 3 (SMYD3) Expression in Gallbladder Cancer: a Pilot Study.

The Suvar, Enhancer of zeste, and Trithorax (SET) and myeloid-Nervy-DEAF-1 (MYND) domain-containing protein 3 (SMYD3) is a histone lysine methyltransferase and has been recently unveiled to play significant roles in the progression of human cancer via regulating various key cancer-associated genes and pathways. The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. SMYD3 expression was evaluated by immunohistochemistry and reverse transcriptase PCR (RT-PCR) from 30 cases each of GBC and cholelithiasis patients. The expression was compared with different clinicopathological parameters. The SMYD3 expression was found to be significantly upregulated in GBC than cholelithiasis group (p < 0.05). The SMYD3 with increased expression level was observed in 73.3% of the GBC cases (p < 0.05). Moreover, mRNA SMYD3 expression was observed in 73.3% of GBC and 10% of control (p < 0.05). Our results indicated that the overexpression of SMYD3 plays an important role in the GBC progression, and SMYD3 may represent useful biomarker for gallbladder cancer patients.

SARS-CoV-2 antibody seroprevalence in India, August-September, 2020: findings from the second nationwide household serosurvey.

BACKGROUND: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. METHODS: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. FINDINGS: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case. INTERPRETATION: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country. FUNDING: Indian Council of Medical Research.

Genetic mutational analysis of ß-catenin gene affecting GSK-3ß phosphorylation plays a role in gallbladder carcinogenesis: Results from a case control study.

This manuscript has reported different mutations of ß-catenin gene in gallbladder cancer patients which affect GSK-3ß phosphorylation site. PURPOSE: Gallbladder carcinoma (GBC) is a relatively rare and fatal cancer with poor prognosis. The molecular mechanism of gallbladder carcinogenesis is still not clear. Wnt signaling pathway is a highly conserved pathway that regulates proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. ß-catenin plays major role in Wnt signaling and aberrations in ß-catenin has found to be involved in several cancers pathogenesis. This study was carried out to document the mutations of ß-catenin gene in gallbladder cancer and to evaluate its possible role in gallbladder carcinogenesis. METHODS: PCR-SSCP (Single Stranded Conformation Polymorphism) for ctnnb1 was performed in 50 patients each of gallbladder cancer, cholelithiasis and 50 healthy controls. Samples that showed variation in banding pattern were sequenced. RESULTS: Variation in banding pattern was observed in 9 (18%) samples of GBC, 4 (8%) of cholelithiasis and 2 (4%) of control. Sequencing analysis showed 9 novel mutations of ctnnb1 in exon 3 in 18% of gallbladder cancer (χ2 = 5.778; p < 0.05). Six point mutations, 1 deletion and 1 insertion mutation were found in 9 cases of gallbladder cancer. All point mutations were mis-sense mutation that affected highly conserved serine or threonine region that is important for GSK-3ß phosphorylation. CONCLUSION: Findings of the study suggests that high frequency of non synonymous mutations of ß-catenin gene (ctnnb1) occurs in patients with gallbladder cancer. As these mutations mainly effect GSK 3ß phosphorylation, it may be concluded that this might be an important step in gallbladder carcinogenesis. These ß-catenin mutations lead to Wnt pathway activation and appear to have a role in progression from inflammation to cancer in gallbladder.

Dysregulated Expression and Subcellular Localization of Base Excision Repair (BER) Pathway Enzymes in Gallbladder Cancer.

Base excision repair (BER) pathway is one of the repair systems that has an impact on radiotherapy and chemotherapy for cancer patients. The molecular pathogenesis of gallbladder cancer is not known extensively. In the present study we investigated whether the expression of AP endonuclease 1 (APE1) and DNA polymerase ß (DNA pol ß), key enzymes of BER pathway has any clinical significance with gallbladder carcinogenesis. 41 gallbladder cancer, 27 chronic cholecystitis, and 3 normal gallbladder specimens were analyzed for the expression of APE1 and DNA polymerase ß by western blotting, and subcellular localization studied by immunohistochemistry. The enzymatic activity of APE1 was also studied. The correlations with expression of the above proteins with clinical-pathological characteristics of gallbladder cancer patients were analyzed. The integrated density value ratio (relative expression) of total APE1 (37 kDa + 35 kDa variant) analyzed in the three groups of tissues, was 0.76±0.03 in normal gallbladder, 0.91±0.08 in chronic cholecystitis, and 1.12±0.05 in gallbladder cancer. APE1 was found to be up-regulated in 80% of gallbladder carcinoma samples (P = 0.01). A positive trend of APE1 expression with tumor stage and lymph node positivity was observed. The enzymatic activity of APE1 was found higher in gallbladder cancer samples in comparison with chronic cholecystitis. The integrated density value ratio of DNA polymerase ß for normal gallbladder, chronic cholecystitis and gallbladder cancer tissue samples were 0.46±0.03, 0.7±0.06 and 1.33±0.1, respectively. DNA polymerase ß was found to be upregulated in almost all gallbladder carcinoma samples (P =0.0001), and its expression was negatively correlated with age (P=0.02). DNA polymerase ß expression showed a positive trend with tumor stage and nuclear differentiation of gallbladder cancer. It may be concluded that alteration of these BER pathway proteins may be the causal factors for carcinogenesis of gallbladder, and has targeted therapeutic potential.

Role of bile bacteria in gallbladder carcinoma.

BACKGROUND/AIMS: Long standing calculus disease has been observed to be a risk factor for gallbladder carcinoma. However it is possible that calculi may be incriminated by some means other than just chronic irritation. Calculi may induce an element of stasis, promoting chronic infection leading to increased turnover of primary bile acids to secondary bile acids, which are known tumor promoters and initiators. This study aimed to find the prevalence of biliary microflora in gallbladder carcinoma and association of gallbladder carcinoma with chronic bacterial infection and bile acid profile. METHODOLOGY: Bile culture was done in 390 patients divided into 3 groups--gallbladder carcinoma 65 (17%), cholelithiasis 125 (32%) and control group 200 (51%). Serum samples were analyzed for presence of Vi antibody for chronic typhoid carrier state and bile acid analysis was done in 10 patients in each group. RESULTS: 116 (30%) patients had culture positive bile. Significantly higher number of patients with gallbladder carcinoma 40 (65%) had culture positive bile as compared to cholelithiasis 52 (42%) and control 24 (12%). Vi Antibodies suggestive of chronic typhoid carrier state were found to be significantly higher in the gallbladder carcinoma group 20 (31%) as compared to controls 22 (11%) (OR 3.596, p < 0.05) however, the difference was statistically insignificant in the cholelithiasis group 12 (11%) (OR 0.859, p > 0.05). There was a 6.84 times higher risk of developing gallbladder carcinoma in culture positive cholelithiasis patients and 5.14 times if both Vi antibody and cultures were positive. Bile analysis showed primary bile acids cholic acid and chenodeoxycholic acid to be lower while secondary bile acids deoxycholic acid and lithocholic acid to be more in the gallbladder carcinoma group (7.268 mg/mL, 9.183 mg/ mL, 14.468 mg/mL, 3.312 mg/mL respectively) than cholelithiasis (17.50 mg/mL, 13.80 mg/mL, 6.07 mg/ mL, 2.05 mg/mL) and control group (19.85 mg/mL, 16.53 mg/mL, 2.71 mg/mL, 1.128 mg/mL respectively). The difference was statistically significant. CONCLUSIONS: Chronic bacterial infection of bile leading to production of carcinogenic precursors might be one of the etiological factors in the pathogenesis of gallbladder carcinoma and hence a target for its prevention.

Repair of uterocutaneous fistula.

BACKGROUND: Uterocutaneous fistula is a rare condition that may be difficult to manage. CASE: A young woman who underwent surgical intervention for cryptomenorrhea 3 years ago developed menstrual discharge from the abdominal scar. A fistulous tract leading from the infraumbilical midline scar to the uterus was demonstrated on contrast study. Genital examination revealed vaginal agenesis. A vaginoplasty was performed as the first stage. This was followed one year later by excision of the fistulous tract and establishment of cervicovaginal communication. The patient is now menstruating from the vaginal passage. CONCLUSION: This case shows that a stepwise, well-planned, and well-executed procedure can lead to a satisfactory repair of an uterocutaneous fistula.

Association of Methylenetetrahydrafolate Reductase Gene Polymorphism (MTHFR) in Patients with Gallbladder Cancer.

PURPOSE: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and plays a major role in DNA methylation. There are two popular MTHFR polymorphisms known as C677T and A1298C which are found to be involved in folate metabolism and lowering the enzyme activity, thus may be linked with cancer development. This study aims to look at the association of these polymorphisms in gallbladder cancer. METHODS: Thirty patients each with gallbladder cancer, cholelithiasis, and normal gallbladder were genotyped for the above-given polymorphisms by PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: C677T MTHFR polymorphism was not associated (χ(2) = 2.44, p = 0.85) with an increased likelihood of having gallbladder cancer. A1298C was significantly associated (χ(2) = 28.87, p < 0.001) with risk of developing gallbladder cancer. A1298C was significantly correlated with grade (r = 0.337, p < 0.001) and histopathology (r = 0.446, p < 0.001). CONCLUSION: This study proposed that MTHFR A1298C polymorphism may be associated with risk of developing gallbladder cancer, and there is no association between C677T polymorphism and gallbladder cancer.

Pain in acute and chronic wounds: a descriptive study.

The significance of pain in wound healing is much neglected because of biases against pain management in general, a lack of knowledge of available analgesics, and difficulties associated with pain measurement. To assess pain in patients suffering from acute and chronic wounds, a 1-day descriptive study was conducted involving 50 patients, 26 with acute wounds and 24 with chronic wounds, served by the wound clinic of a university hospital. Patients responded to questions regarding onset, location, type, and intensity of pain using the Visual Analog and Visual Reporting Scales and to statements about aggravating and relieving factors and overall impact on their quality of life using a 5-point scale where 5 = totally agree and 1 = completely disagree. Results showed pain was commonly mild to moderate (41 patients, 88%), located in and around wound (43 patients, 93.5%), occurred most frequently during dressing change (30 patients, 65%), and was relieved by medications (39 patients, 84.8%) and positioning (17 patients, 37%). The most commonly affected quality of life variables were physical activity (40 patients, 87% of patients) and social functioning (23 patients, 50%). Controlling wound pain can play a major role in improving patient quality of life.