Site-Selective Biofunctionalization of 3D Microstructures Via Direct Ink Writing.

Two-photon lithography has revolutionized multi-photon 3D laser printing, enabling precise fabrication of micro- and nanoscale structures. Despite many advancements, challenges still persist, particularly in biofunctionalization of 3D microstructures. This study introduces a novel approach combining two-photon lithography with scanning probe lithography for post-functionalization of 3D microstructures overcoming limitations in achieving spatially controlled biomolecule distribution. The method utilizes a diverse range of biomolecule inks, including phospholipids, and two different proteins, introducing high spatial resolution and distinct functionalization on separate areas of the same microstructure. The surfaces of 3D microstructures are treated using bovine serum albumin and/or 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) to enhance ink retention. The study further demonstrates different strategies to create binding sites for cells by integrating different biomolecules, showcasing the potential for customized 3D cell microenvironments. Specific cell adhesion onto functionalized 3D microscaffolds is demonstrated, which paves the way for diverse applications in tissue engineering, biointerfacing with electronic devices and biomimetic modeling.

3D Nanolithography by Means of Lipid Ink Spreading Inhibition.

While patterning 2D metallic nanostructures are well established through different techniques, 3D printing still constitutes a major bottleneck on the way to device miniaturization. In this work a fluid phase phospholipid ink is used as a building block for structuring with dip-pen nanolithography. Following a bioinspired approach that relies on ink-spreading inhibition, two processes are presented to build 2D and 3D metallic structures. Serum albumin, a widely used protein with an innate capability to bind to lipids, is the key in both processes. Covering the sample surface with it prior to lipid writing, anchors lipids on the substrate, which ultimately allows the creation of highly stable 3D lipid-based scaffolds to build metallic structures.

Clinical Characteristics and Remedy Profiles of Patients with COVID-19: A Retrospective Cohort Study.

OBJECTIVE: The aim of the study was to identify indicated homeopathic remedies based on the clinical characteristics of coronavirus disease 2019 (COVID-19) patients in India. METHODS: In this retrospective, cohort study, confirmed COVID-19 patients admitted at a COVID Health Centre in New Delhi between April 29 and June 17, 2020 were given conventional and homeopathic treatment. Patients were grouped into mild, moderate or severe categories of disease. Their symptomatologic profiles were analyzed to identify indicated homeopathic medicines. RESULTS: A total of 196 COVID-19 patients were admitted. One hundred and seventy-eight patients had mild symptoms; eighteen patients had moderate symptoms; no patients with severe symptoms were included as they were referred to tertiary care centers with ventilatory support. The mean age of patients with mild symptoms was significantly lower (38.6 years; standard deviation or SD ± 15.8) compared with patients in the moderate category (66.0 years; SD ± 9.09). The most important symptoms identified were fever (43.4%), cough (47.4%), sore throat (29.6%), headache (18.4%), myalgia (17.9%), fatigue (16.8%), chest discomfort (13.8%), chills (12.6%), shortness of breath (11.2%) and loss of taste (10.2%). Twenty-eight homeopathic medicines were prescribed, the most frequently indicated being Bryonia alba (33.3%), Arsenicum album (18.1%), Pulsatilla nigricans (13.8%), Nux vomica (8%), Rhus toxicodendron (7.2%) and Gelsemium sempervirens (5.8%), in 30C potency. CONCLUSION: Data from the current study reveal that Arsenicum album, Bryonia alba, Pulsatilla nigricans, Nux vomica, Rhus toxicodendron and Gelsemium sempervirens are the most frequently indicated homeopathic medicines. A randomized controlled clinical trial based on this finding is the next step.

Force model for laparoscopic graspers: implications for virtual simulator design.

INTRODUCTION: Laparoscopic graspers limit haptic perception, which in turn leads to tissue damage. Using virtual simulators to train surgeons in handling these instruments would ensure safer grasp. The design of a laparoscopic virtual simulator with force feedback depends on effective implementation of the grasper force model. OBJECTIVE: To develop a laparoscopic grasper tip force model theoretically from grasper mechanics and validate the same experimentally during laparoscopic pinching. MATERIALS AND METHODS: We developed a force model for double and single jaw action graspers using grasper mechanics. For experimental validation, the handle angle and the forces at the tip and the handle of the instrumented graspers during laparoscopic pinching of porcine abdominal tissues were measured. The intra-class correlation coefficient (ICC) between experimental and calculated tip force was calculated. RESULT: Excellent ICC (ICC ≥0.8, p<.001) between calculated and experimental tip force was obtained for both graspers for all grasped tissues. Mean absolute forces for all trials while using double and single jaw action graspers were ((FTc = 1.7N, FTe = 1.8N) and (FTc = 2.2N, FTe = 2.8N)) for gall bladder, ((FTc = 3.4N, FTe = 4.4N) and (FTc = 3.3N, FTe = 3.4N)) for liver and ((FTc = 4.2N, FTe = 4.5N) and (FTc = 2.3N, FTe = 2.6N)) for spleen, respectively. CONCLUSION: The proposed model may be used for the design of laparoscopic pinching action in a virtual simulator with force feedback and also for better ergonomic design of laparoscopic graspers.

Free-breathing myocardial T2* mapping using GRE-EPI and automatic non-rigid motion correction.

BACKGROUND: Measurement of myocardial T2* is becoming widely used in the assessment of patients at risk for cardiac iron overload. The conventional breath-hold, ECG-triggered, segmented, multi-echo gradient echo (MGRE) sequence used for myocardial T2* quantification is very sensitive to respiratory motion and may not be feasible in patients who are unable to breath-hold. We propose a free-breathing myocardial T2* mapping approach that combines a single-shot gradient-echo echo-planar imaging (GRE-EPI) sequence for T2*-weighted image acquisition with automatic non-rigid motion correction (MOCO) of respiratory motion between single-shot images. METHODS: ECG-triggered T2*-weighted images at different echo times were acquired by a black-blood, single-shot GRE-EPI sequence during free-breathing. A single image at a single TE is acquired in each heartbeat. Automatic non-rigid MOCO was applied to correct for in-plane respiratory motion before pixel-wise T2* mapping. In a total of 117 patients referred for clinical cardiac magnetic resonance exams, the free-breathing MOCO GRE-EPI sequence was compared to the breath-hold segmented MGRE approach. Image quality was scored independently by 2 experienced observers blinded to the particular image acquisition strategy. T2* measurements in the interventricular septum and in the liver were compared for the two methods in all cases with adequate image quality. RESULTS: T2* maps were acquired in all 117 patients using the breath-hold MGRE and the free-breathing MOCO GRE-EPI approaches, including 8 patients with myocardial iron overload and 25 patients with hepatic iron overload. The mean image quality of the free-breathing MOCO GRE-EPI images was scored significantly higher than that of the breath-hold MGRE images by both reviewers. Out of the 117 studies, 21 breath-hold MGRE studies (17.9% of all the patients) were scored to be less than adequate or very poor by both reviewers, while only 2 free-breathing MOCO GRE-EPI studies were scored to be less than adequate image quality. In a comparative evaluation of the images with at least adequate quality, the intra-class correlation coefficients for myocardial and liver T2* were 0.868 and 0.986 respectively (p < 0.001), indicating that the T2* measured by breath-hold MGRE and free-breathing MOCO GRE-EPI were in close agreement. The coefficient of variation between the breath-hold and free-breathing approaches for myocardial and liver T2* were 9.88% and 9.38% respectively. Bland-Altman plots demonstrated good absolute agreement of T2* in the interventricular septum and the liver from the free-breathing and breath-hold approaches (mean differences -0.03 and 0.16 ms, respectively). CONCLUSION: The free-breathing approach described for T2* mapping using MOCO GRE-EPI enables accurate myocardial and liver T2* measurements and is insensitive to respiratory motion.

Faculty development to enhance humanistic teaching and role modeling: a collaborative study at eight institutions.

BACKGROUND: There is increased emphasis on practicing humanism in medicine but explicit methods for faculty development in humanism are rare. OBJECTIVE: We sought to demonstrate improved faculty teaching and role modeling of humanistic and professional values by participants in a multi-institutional faculty development program as rated by their learners in clinical settings compared to contemporaneous controls. DESIGN: Blinded learners in clinical settings rated their clinical teachers, either participants or controls, on the previously validated 10-item Humanistic Teaching Practices Effectiveness (HTPE) questionnaire. PARTICIPANTS: Groups of 7-9 participants at 8 academic medical centers completed an 18-month faculty development program. Participating faculty were chosen by program facilitators at each institution on the basis of being promising teachers, willing to participate in the longitudinal faculty development program. INTERVENTION: Our 18-month curriculum combined experiential learning of teaching skills with critical reflection using appreciative inquiry narratives about their experiences as teachers and other reflective discussions. MAIN MEASURES: The main outcome was the aggregate score of the ten items on the questionnaire at all institutions. KEY RESULTS: The aggregate score favored participants over controls (P = 0.019) independently of gender, experience on faculty, specialty area, and/or overall teaching skills. CONCLUSIONS: Longitudinal, intensive faculty development that employs experiential learning and critical reflection likely enhances humanistic teaching and role modeling. Almost all participants completed the program. Results are generalizable to other schools.

High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia.

BACKGROUND: The Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP) region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations. RESULTS: The predominant HBV genotype among the Minangkabau HBV carriers (n=117) was C (72.6%) followed by B (24.8%) and co-infection with B and C (2.6%). The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively). From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7. CONCLUSION: HBV/C with subgenotype C1 was the predominant HBV genotype among HBV carriers of Minangkabau ethnicity. The prevalence of pre-S, A1762T/G1764A, and T1753V mutations was higher among the Minangkabau compared to Indonesian HBV carriers in general.

Extended multiorgan resection in locally advanced gastric cancer: a single centre experience from south India.

BACKGROUND: The prognostic and survival benefit of extended multiorgan resection for locally advanced gastric adenocarcinoma remains controversial. The morbidity associated with additional organ resection has been found to be higher when compared to patients undergoing gastrectomy alone. The aim of our study was to evaluate the morbidity, mortality and survival benefit associated with extended multiorgan resection for locally advanced gastric adenocarcinoma. METHODS: From January 2004 to December 2011, 721 patients underwent resectional surgery for gastric adenocarcinoma at the Christian Medical College, Vellore, India. Out of this group, 36 patients underwent primary resection and had one or more organs resected in addition to the stomach. A retrospective analysis of the case records of all these patients was performed. The Kaplan-Meier survival probability was estimated. Cox regression analysis was used to evaluate the clinico-pathological variables affecting the survival of these patients. RESULTS: The perioperative morbidity and mortality rates were 25% and 5.5% respectively. The most common organs resected were colon and spleen. The incidence of pathologically confirmed T4b cancers was only 50%. The median survival of these patients was 28 months. The survival was influenced by a R0 or curative resection. However, it was not statistically significant. CONCLUSION: Extended multiorganresection in locally advanced gastric cancer can be performed with acceptable morbidity and mortality. In our study, overstaging was found in 50% of the patients and hence, when the real nature of invasion is unclear, the surgeon may proceed with en bloc resection of the stomach with the involved adjacent organs. As long as an R0 resection can be achieved, extended multiorgan resection can be performed for carcinoma stomach.

Point-Of-Care Ultra-Sound (POCUS) for suspected surgical abdominal conditions in rural India-a mixed-method health needs assessment.

INTRODUCTION: Evidence has shown a trend towards rising mortality from surgical abdominal conditions with increasing distance from hospitals in Eastern India. It has been claimed that imaging modalities such as portable ultrasound are ideal for use in rural areas of developing countries for diagnosis and management of a variety of acute abdominal conditions. This mixed-methods study aimed to explore the need for increased access to POCUS in rural, hard-to-reach populations within India, and to identify barriers that may exist to increasing this access. METHODS: This mixed-methods study utilized a health needs assessment framework. Quantitative data was extracted from medical records within two outreach camp organisations supporting hard-to-reach populations in Uttarakhand and Jharkhand to provide contextual background statistics. Qualitative data was collected using semi-structured interviews taken from employees of each outreach camp. A framework analysis was employed to analyse the qualitative data. Both datasets were analysed in parallel. RESULTS: Twelve semi-structured interviews were undertaken, and 3 months of medical records were reviewed. Themes that presented themselves from the data included the use of camps for case-finding of conditions amenable to routine surgery, a need for POCUS to help with this diagnostic process, a perceived high disease burden from renal calculi, and complex cultural and legislative barriers to POCUS specific to this setting. DISCUSSION: POCUS was considered a useful tool in expanding access to surgery for these settings and finding ways of overcoming cultural and legislative barriers to its use should be of high priority. POCUS should be highly portable, robust, easily repairable, and battery operated. For telemedicine to be fully utilised, signal quality will have to be proven to be reliable.

Uterine tumor resembling ovarian sex-cord tumor - a rare gynecological neoplasm.

Uterine tumor resembling ovarian sex-cord tumor is a rare group of uterine neoplasms with unknown histogenesis and differentiation towards ovarian sex-cord elements. They are benign in nature with low malignancy potential. Diagnosis is based on immunohistochemistry and morphological features, and the distinction from other more malignant differentials is paramount to correctly individualizing treatment.

Fully-modelled blood-focused variable inversion times for 3D late gadolinium-enhanced imaging.

PURPOSE: Variable heart rate during single-cycle inversion-recovery Late Gadolinium-Enhanced (LGE) scanning degrades image quality, which can be mitigated using Variable Inversion Times (VTIs) in real-time response to R-R interval changes. We investigate in vivo and in simulations an extension of a single-cycle VTI method previously applied in 3D LGE imaging, that now fully models the longitudinal magnetisation (fmVTI). METHODS: The VTI and fmVTI methods were used to perform 3D LGE scans for 28 3D LGE patients, with qualitative image quality scores assigned for left atrial wall clarity and total ghosting. Accompanying simulations of numerical phantom images were assessed in terms of ghosting of normal myocardium, blood, and myocardial scar. RESULTS: The numerical simulations for fmVTI showed a significant decrease in blood ghosting (VTI: 410 ± 710, fmVTI: 68 ± 40, p < 0.0005) and scar ghosting (VTI: 830 ± 1300, fmVTI: 510 ± 730, p < 0.02). Despite this, there was no significant change in qualitative image quality scores, either for left atrial wall clarity (VTI: 2.0 ± 1.0, fmVTI: 1.8 ± 1.0, p > 0.1) or for total ghosting (VTI: 1.9 ± 1.0, fmVTI: 2.0 ± 1.0, p > 0.7). CONCLUSIONS: Simulations indicated reduced ghosting with the fmVTI method, due to reduced Mz variability in the blood signal. However, other sources of phase-encode ghosting and blurring appeared to dominate and obscure this finding in the patient studies available.

Interval estimation of familial correlations from pedigrees.

We study the estimation of familial correlations from pedigree data without the assumption of multivariate normality, using asymptotic results to obtain standard errors and confidence intervals. Two extreme weights that can be given to pairs of observations from relatives in pedigrees are pair-wise weights, in which each pair is given the same weight, and uniform weights, in which each pedigree is given the same weight. A best weighted average of these two estimates for a particular correlation as well as its standard error are derived using quadratic models for the estimates and their variances. Conclusions regarding the adequacy of the method in terms of bias, absolute bias, variance, and confidence interval coverage probabilities are presented on the basis of results from simulation studies. We determine under what circumstances the nominal 95 percent confidence intervals have excellent average coverage of the true values even for samples of small size and under what circumstances the results must be viewed with caution. We then describe a procedure by which, for both small family and large family structures, we find that the estimates we recommend provide accurate results.

Disseminated angiosarcoma of the dialysis fistula in 2 patients without kidney transplants.

Angiosarcoma of the dialysis fistula is a rare occurrence. Of the 8 cases of angiosarcoma of the dialysis fistula reported in the literature, all occurred after kidney transplant and long-term immunosuppression therapy. We report 2 cases of disseminated angiosarcoma of the dialysis fistula in hemodialysis patients without concurrent kidney transplants or immunosuppression. Both patients presented with symptoms of pain and bleeding at the site of the thrombosed fistula. Clinicians should be aware that angiosarcoma of the dialysis fistula can occur in patients without kidney transplants.

Detection and survival of colorectal cancer from a 2 week wait service.

AIM: To determine detection strategies for colorectal cancer (CRC) and to analyse subsequent survival from a 2 week wait (2WW) service. METHOD: Retrospective analysis of 2WW and hospital CRC databases from January 2006 to July 2009. Survival was assessed using Kaplan Meier survival curves and Cox's proportional hazard models. Proximal cancers were those proximal to and including the splenic flexure. RESULTS: From 1725 patients seen in a 2WW clinic, 108 were identified with CRC. Median follow-up in survivors was 514 days (interquartile range 160-788 days). Of 23 patients investigated for iron deficient anaemia and/or abdominal mass, 78% (18) were found to have proximal cancers. Of 85 patients with symptoms of change in bowel habit, rectal bleeding or abdominal pain, 15% (13) were found to have proximal cancers. Age, haemoglobin and mean corpuscular volumes between these 13 patients and the 72 distal cancers in this group were not significantly different. Multivariable analysis showed that survival was lower for those presenting with proximal cancers (hazard ratio 2.912, 95% confidence interval 1.361-6.227, p=0.006) and for those with increasing Dukes stage (p<0.001). CONCLUSIONS: Flexible sigmoidoscopy would have missed 15% of cancers in those presenting with symptoms alone. Patients with proximal tumours had a worse prognosis. Further research is needed to identify those presenting with symptoms alone who are at high risk of having proximal tumours and thus requiring whole colonic imaging.

Tracheal injury during oesophagectomy--incidence, treatment and outcome.

BACKGROUND AND AIM: Iatrogenic tracheal injuries are uncommon, potentially lethal and associated with significant morbidity. In this report we analyze the incidence of iatrogenic tracheobronchial injuries sustained during oesophagectomies and the results and outcome of repair using a pedicled intercostal muscle flap. METHODS: A retrospective analysis was done on all patients who underwent an oesophagectomy between June 2000 and May 2011. Data was collected from an electronic database and the medical records of patients, maintained at our hospital. RESULTS: One hundred and fourteen patient records were analyzed. There were 85 male and 29 female patients. Their mean age was 47 years (range 16 to 86 years). Forty two (36%) underwent a transhiatal oesophagectomy, 34 (31%) Mckeown's oesophagectomy, 35 (31%) Ivor Lewis oesophagectomy and 3 (2%) thoracoscopy assisted oesophagectomy. Of the 114 oesophagectomies, 86 (75%) were performed for malignant and 28 (25%) for benign pathologies (benign tumors and corrosive strictures of the esophagus). In our study, four patients sustained injury to the tracheobronchial tree during oesophagectomy. In patients who sustained injury during a transhiatal dissection a right anterolateral thoracotomy was made. All injuries in the thoracic tracheobronchial tree were repaired primarily and reinforced with an intercostal muscle flap. In the patient with injury to the cervical part of the trachea, repair was done primarily and reinforced with cyanoacrylate glue. All patients who sustained injury had malignancy and three patients had received neoadjuvant chemoradiotherapy. Two patients sustained injury during transhiatal oesophagectomy and two during a Mckeown's oesophagectomy. There was one mortality which was due to ventilator associated pneumonia and related complications. The remaining three were alive with no evidence of repair breakdown. CONCLUSIONS: Iatrogenic tracheal injuries are uncommon complications but associated with significant morbidity. Preoperative chemoradiotherapy and malignancy are risk factors for iatrogenic tracheal injuries. Reinforcement of the suture line with a muscle flap is an effective technique of repair. Prompt ontable identification and adequate surgical treatment is necessary for a good outcome.

Pattern of maxillofacial fractures at a tertiary hospital in northern India: a 4-year retrospective study of 718 patients.

PURPOSE: Pattern and aetiology of maxillofacial injuries varies from one country to another and even within the same country depending on prevailing socio-economic, cultural and environmental factors. Various studies have been carried out in various countries to study the epidemiology and demographics of the maxillofacial injuries but the studies from India are few. MATERIAL AND METHODS: Retrospective study was undertaken at Christian Medical College Ludhiana (India) from January 2006 to December 2009. Treatment records of the patients was checked and age, gender, aetiology of injury, associated injuries, maxillofacial fractures and treatment offered were recorded. RESULTS: A total of 1075 fractures were recorded in 718 patients, ranging from 11 months to 85 years of age. Male:female ratio was 6.6:1. Maxillofacial injuries were most common in third decade of life. A total of 517 patients suffered injuries because of road traffic accident, 115 because of accidental fall and 67 because of interpersonal violence. A total of 184 patients had 221 associated injuries of which 56.1% head injuries, 29.0% orthopaedic injuries and 14.9% other injuries were present. Of 596 middle third fractures, 29.8% were managed conservatively; for 21.7% and 48.7% of fractures, closed reduction and open reduction were performed respectively. Of 479 mandibular fractures, 1.8% was managed conservatively; for 16.7% and 81.5% fractures, closed reduction and open reduction were performed respectively. CONCLUSION: Better socio-economic status of people, increased vehicular movements and non-implementation of road safety norms have increased road traffic accidents. Proper education of the people who are most commonly involved in the RTA can be one of the possible ways to reduce the maxillofacial injuries.

Multiscale Adaptive Search.

We present a continuous-space multiscale adaptive search (MAS) algorithm for single or multiple searchers that finds a stationary target in the presence of uncertainty in sensor diameter. The considered uncertainty simulates the influence of the changing environment and terrain as well as adversarial actions that can occur in practical applications. When available, information about the foliage areas and a priori distribution of the target position is included in the MAS algorithm. By adapting to various uncertainties, MAS algorithm reduces the median search time to find the target with a probability of detection of at least PD and a probability of false alarm of at most PFA. We prove that MAS algorithm discovers the target with the desired performance bounds PD and PFA. The unique features of the MAS algorithm are realistic second-order dynamics of the mobile sensors that guarantees uniform coverage of the surveyed area and a two-step Neyman-Pearson-based decision-making process. Computer simulations show that MAS algorithm performs significantly better than lawnmower-type search and billiard-type random search. Our tests suggest that the median search time in the MAS algorithm may be inversely proportional to the number of participating searchers. As opposed to lawnmower search, the median search time in the MAS algorithm depends only logarithmically on the magnitude of uncertainty.

Genetic risk factors for colorectal cancer in multiethnic Indonesians.

Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

Toponome imaging system: in situ protein network mapping in normal and cancerous colon from the same patient reveals more than five-thousand cancer specific protein clusters and their subcellular annotation by using a three symbol code.

In a proof of principle study, we have applied an automated fluorescence toponome imaging system (TIS) to examine whether TIS can find protein network structures, distinguishing cancerous from normal colon tissue present in a surgical sample from the same patient. By using a three symbol code and a power of combinatorial molecular discrimination (PCMD) of 2(21) per subcellular data point in one single tissue section, we demonstrate an in situ protein network structure, visualized as a mosaic of 6813 protein clusters (combinatorial molecular phenotype or CMPs), in the cancerous part of the colon. By contrast, in the histologically normal colon, TIS identifies nearly 5 times the number of protein clusters as compared to the cancerous part (32 009). By subcellular visualization procedures, we found that many cell surface membrane molecules were closely associated with the cell cytoskeleton as unique CMPs in the normal part of the colon, while the same molecules were disassembled in the cancerous part, suggesting the presence of dysfunctional cytoskeleton-membrane complexes. As expected, glandular and stromal cell signatures were found, but interestingly also found were potentially TIS signatures identifying a very restricted subset of cells expressing several putative stem cell markers, all restricted to the cancerous tissue. The detection of these signatures is based on the extreme searching depth, high degree of dimensionality, and subcellular resolution capacity of TIS. These findings provide the technological rationale for the feasibility of a complete colon cancer toponome to be established by massive parallel high throughput/high content TIS mapping.

Endovenous laser therapy in the treatment of lower-limb venous ulcers.

PURPOSE: To assess the efficacy of endovenous laser therapy (EVLT) in the treatment of lower-limb venous ulcers secondary to venous reflux. MATERIALS AND METHODS: Forty-four of 139 patients referred for EVLT from January 2004 to August 2007 had nonhealing venous ulcers. Preprocedural duplex ultrasound (US) was performed to document saphenous venous reflux secondary to saphenofemoral/saphenopopliteal junction incompetence, deep venous insufficiency, and deep vein thrombosis. Follow-up intervals were within 1 week, monthly until ulcer healing, and every 6 months thereafter. Mean follow-up period was 35.8 months (range, 8.1-59.3 months). RESULTS: Mean great saphenous vein (GSV) diameter and length treated were 9.9 mm (range, 5.5-16.0 mm) and 36.7 cm (range, 20.0-60.0 cm). Mean laser energy used was 3,292 J (range, 1,392-4,971 J). Mean energy deposited per centimeter of vein was 93.6 J/cm (range, 45.2-182.0 J/cm). Mean laser time was 232 seconds (range, 99-347 sec). Fifteen patients with follow-up duplex US had no GSV flow at 6 months, with nonvisualization indicating complete obliteration. Ulcer healing occurred as early as 1 week after the procedure in some patients. Cumulative healing rates at 1, 3, 6, and 12 months were 82.1%, 92.5%, 92.5%, and 97.4%, respectively. No ulcer had recurred at 1 year, but ulcers recurred in five patients at 14, 14, 23, 35, and 52 months after EVLT, respectively. One patient with a nonhealing ulcer 2 years after treatment developed well differentiated squamous cell carcinoma. CONCLUSIONS: Ulcer epithelization occurred with continued GSV occlusion and loss of flow. Most ulcers healed within 3 months with no recurrence at 1 year. Nonhealing ulcers should undergo biopsy to exclude malignant transformation.