Perspectives of colon-specific drug delivery in the management of morning symptoms of rheumatoid arthritis.

Rheumatoid arthritis is a chronic condition that is characterized by joint pain and inflammation. It is an autoimmune disorder in which the body tissues are erroneously attacked by the immune system of the host itself. It has been evident that rheumatoid arthritis symptoms follow a 24 h circadian rhythm and exhibit high thresholds of pain, functional disability, and stiffness predominantly early in the morning. Colon-specific drug delivery systems can be utilized in the formulations to be used in the treatment of rheumatoid arthritis. The colon-specific drug delivery system has shown promising results in the treatment of different diseases at the colonic site like Crohn's disease, ulcerative colitis, colon cancer, etc. The colon-specific drug delivery is capable of delivering the formulation at the predetermined location and predetermined time. The early morning symptoms of rheumatoid arthritis like pain and inflammation can be treated using the various approaches of the colon-specific drug delivery system because it will lead to patient compliance as the patient will not require administering the formulation immediately after waking up in the morning. This review also explains the immunological factors which may trigger rheumatoid arthritis in human beings. It further explores conventional approaches like pH-dependant, microorganisms-driven, pressure-controlled, and time-dependant formulations. By employing two or more conventional approaches given above the various novel approaches have been designed to eliminate the drawbacks of individual techniques.

Molecular characterization of diarrheagenic Escherichia coli pathotypes: Association of virulent genes, serogroups, and antibiotic resistance among moderate-to-severe diarrhea patients.

BACKGROUND: Diarrheagenic Escherichia coli (DEC) signifies as an important etiological agent of moderate-to-severe diarrhea. This study was primarily focused on molecular identification of DEC pathotypes; their association with serogroups and estimates of resistance profiles against different antibiotics regime. METHODS: Five hundred seventy-two stool specimens from diarrhea patients were investigated for DEC pathotypes. Molecular pathotypes were identified by amplification of virulence genes associated with distinct pathotypes followed by sequencing. Diarrhea is a self-limiting disease, however, severity and persistence of infection suggest antibiotic use. Therefore, AST and MIC were determined against common antibiotic regimen. Correlations between molecular pathotypes and serogroups were analyzed by somatic "O" antigen serotyping. RESULTS: The present findings reveal incidence of DEC as an etiological agent up to a level of 21% among all diarrheal age groups. DEC infection rate was higher in children. Enteropathogenic E. coliEPEC, a molecular pathotype of DEC, was found as a predominant pathotype with highest frequency of 13.7%. Two other molecular pathotypes enterotoxigenic E. coli (ETEC) and enteroaggregative E. coli (EAEC) accounted for 5.7% and 1.3%, respectively for all diarrhea incidences. Serological analysis deciphered somatic antigens O26, O2, and O3 as major serogroups identified among EPEC, ETEC, and EAEC pathotypes, respectively. All DEC pathotypes exhibited high levels of antibiotic resistance except for cotrimoxazole and norfloxacin. CONCLUSION: Comprehensive molecular characterization of DEC pathotypes, their incidence estimates, and antibiogram patterns will help in ascertaining better diagnostic and therapeutic measures in management of diarrheal diseases.

Socio-economical and Clinico-Radiological Profile of 474 MDR TB Cases of a Rural Medical College.

OBJECTIVE: To study the socio economical and clinico radiological profile of 474 diagnosed MDR TB cases who came for the initiation of MDR TB regimen in DRTB center of R.D.Gardi Medical college, Ujjain. METHODOLOGY: This is a retrospective and prospective observational study for a total period of three years from October 2013 to September 2016. The patients were evaluated clinically, radiologically and were investigated thoroughly according to PMDT guidelines and then were started on MDR TB treatment. The study was conducted at drug resistance tuberculosis center (DR-TB) managed by department of Pulmonary Medicine. RESULTS: 474 cases were included in the study and we found that patients were in the age range of 10-84 years, maximum patients were in age group of 30 to 39 years, and mean age was 38 yrs. Male to female ratio was 2.73 to 1, most of the patients in the study were from rural area i.e. 61.6%. Illiteracy was found in 339 (71.5%) cases and out of these 339, 165 patients (48.6%) were defaulter, 101(29.8%) are cases of relapse, 39(11.5%) were failure, 34(10.02%) of new cases. Maximum numbers of patient were in lower class accounting 63.7% and upper lower class 31.6%, lower middle class only 4.5%. Study also showed mean BMI was 14.9 kg/m2 (range 5.7-25.4 kg/m2), 88.6% of patients were undernourished with BMI less then 18.5kg/m2 .The most common symptoms was cough seen in 96%, followed by fever 67.5%, Dyspnea 52.7%, Anorexia 26.2%, chest pain in 19.8% and least common was haemoptysis seen in 7.6% of patient. Common co-morbidities with MDR-TB found was anemia in 176 out of 474 (i.e.37.1%), 123(25.9%) COPD. Radiological severity showed 219(46.2%) moderate lesion, 139 (29.3%) mild, 107(22.6%) extensive lesion and 9(1.9%) normal, 312(65.8%) of patient are non-cavitory and 162 (34.2%) are cavitory in which 99 (20.9%) were unilateral and 63(13.3%) are bilateral cavitory lesion. Defaulter are most common accounting of 218(46.0%), relapse139 (29.3%) and failure 68 (14.3%), new 48 (10.2%), most of them had taken more than one episode of ATT (72.8%). Most common source of ATT taken by patient is RNTCP it accounts 424 (89.5%) and 46 (9.7%) from private. 181 out of 474 (38.2%) cases delayed the treatment for 1-7 days, 82 out of 474 (17.3%) cases delayed treatment for 8-10 days, 96 out of 474 (20.3%) cases delayed treatment for 11-19 days and 115 out of 474 delayed the treatment for more than 19 days. 95 out of 474 cases i.e. 20.1% cases come from more than 150 km away from their residing area for the initiation of treatment. CONCLUSION: The epidemiological picture of TB showed that males were predominant in our study however female were more affected in younger age group compared to male. More than 51% of the cases were in productive age group which affects the socioeconomic condition of family and society. More than 2/3 of patients were from lower socioeconomic group with low BMI. Therefore improving nutrition and immunity can play an important role. 2.3% of the cases were HIV reactive and were on ART. Co-morbidities like COPD and Diabetes were seen in our study which were statistically significant and had impact on the treatment outcome of results. Significant delay in initiation of MDR-TB regimen from date of DST was seen in 24.3% cases which is matter of concern. Most of the patients had taken ATT from RNTCP in which Defaulter and relapse was major contributor of MDR-TB suspect in our study and patient taking ATT privately were less. Large number of cases which resides more than 150 kilometers from DRTB center initiated the drug after a gap of more than 19 days from the date of DST.

Dengue Fever as a Rare Cause of Acute Pancreatitis.

Dengue is an arthropod borne viral infection endemic in tropical and subtropical climate. Here we report an unusual presentation of Dengue fever as acute pancreatitis. Timely recognition of such atypical complication can reduce the morbidity and mortality.

Severe Hyponatremia as an Uncommon Presenting Feature of Pituitary Macroadenoma.

Hyponatremia is a common electrolyte disturbance, but less commonly utilized and require a thorough evaluation to unmask etiology. It has variety of causes and is rarely due to hypopituitarism. Hyponatremia is a very early complication of pituitary tumor. Here, we report a case, who presented to us with hyponatremia and eventually thorough work-up led us to a diagnosis of Non-functioning pituitary macroadenoma.

Molecular Analysis of VP7 Gene of Rotavirus G1 Strains Isolated from North India.

Rotavirus G1 strains are the predominant cause of diarrhoea in children. Universally common rotavirus vaccines (Rotarix and RotaTeq) include G1 as the immunological component. India has recently introduced rotavirus vaccine in Universal Immunization Programme. Therefore, in the present study, VP7 gene of rotavirus G1 strains circulating in Himachal Pradesh, India is analysed to study their phylogenetic characteristics, and further comparative analysis was performed for assessment of their divergence from the vaccine strains. The rotavirus strains (JU-SOL-5, JU-SOL-58, JU-SOL-77, JU-SOL-173 and JU-SHI-14) analysed in the study were isolated from the faeces of diarrhoeic children during active surveillance for rotaviruses. The Himachal strains clustered together in G1-Lineage 1 in the phylogenetic analysis. All five isolates showed 96.4-98.8 % similarity with the other G1-Lineage 1 strains at amino acid level. However, none of them clustered in the pre-defined sublineages within lineage 1. Interestingly, all the strains were distantly related to the vaccine strains having 93.9-94.5 and 91.9-92.6 % similarities at amino acid level with Rotarix and RotaTeq strains, respectively. The comparative sequence and structural analysis of the Himachal strains with vaccine strains revealed differences in amino acids in epitope region of the protein especially at the antibody neutralization sites. The study highlights variations between the G1 strains from Himachal Pradesh, India and Rotarix and RotaTeq vaccine strains. These differences might have an impact on the neutralization efficiency of vaccine and subsequently on vaccine efficacy. This underscores further investigation to study intragenotype antigenic variability and also impact of viral evolution on vaccine effectiveness.

Ophthalmic Complications in Maxillofacial Trauma: A Prospective Study.

OBJECTIVES: To determine the incidence and types of ophthalmic complications associated with maxillofacial trauma over a period of 24 months. METHODS: An institutional prospective study was conducted on 62 patients presenting with maxillofacial trauma to study the correlation between facial trauma and ophthalmic complications. RESULTS: Road traffic accidents were reported to be the primary etiologic factor for most trauma cases studied. Zygomaticomaxillary complex (ZMC) fracture was associated with more ophthalmic complications while fractures involving the orbital rims and walls were associated with severe complications. CONCLUSIONS: Maxillofacial trauma, particularly those associated with midface, including ZMC fracture, Le Fort II, Le Fort III, and naso-orbito-ethmoidal fractures, can commonly cause ophthalmic complications and blindness in rare cases. Hence, every patient with maxillofacial trauma should undergo an ophthalmic examination and should be placed under close observation for necessary treatment when required.

Prevalence and risk factor assessment of digital eye strain among children using online e-learning during the COVID-19 pandemic: Digital eye strain among kids (DESK study-1).

Purpose: The aim of this study was to determine prevalence, symptoms frequency and associated risk factors of digital eye strain (DES) among children attending online classes during COVID-19 pandemic. Methods: The online electronic survey form was prepared on the Google app. Children/parents were asked to indicate the total duration of digital device use before and during COVID era. The symptoms of DES, its severity and frequency were recorded & measured with the Computer Vision Syndrome Questionnaire. Results: Two hundred and sixty one parents responded to the questionnaire, of these 217 were complete. Mean age of children was 13 ± 2.45 years. Mean duration of digital device used during COVID era was 3.9 ± 1.9 h which is more than pre COVID era (1.9 ± 1.1 h, P = <0.0001). 36.9% (n = 80) were using digital devices >5 h in COVID era as compared to 1.8% (n = 4) before COVID era. The most common digital device used were smartphones (n = 134, 61.7%). One hundred and eight children (49.8%) were attending online classes for >2 h per day. Prevalence of DES in our cohort is 50.23% (109/217). Of these 26.3% were mild, 12.9% moderate and 11.1% of severe grade. Most common symptoms were itching and headache (n = 117, 53.9%). Multivariate analysis revealed age >14 years (P = 0.04), male gender (P = 0.0004), smartphone use (P = 0.003), use of device >5 h (P = 0.0007) and mobile games >1 h/day (P = 0.0001) as independent risk factors for DES in children. Conclusion: There is an increased prevalence of DES among children in COVID era. Parents should be considerate about duration, type and distance of digital device use to avoid DES symptoms in children.

Rugae patterns as an adjunct to sex differentiation in forensic identification.

The aim of the study was to identify the different patterns of palatal rugae and gender differences in rugae pattern in Maharashtra population thereby highlighting the importance of palatal rugae in establishing person's identity. The 600 dental casts of age 18 years and above were included in the study. The rugae were delineated using a sharp graphite pencil under adequate light and magnification and information was recorded about shape, number, size and direction of the palatal rugae. The most commonly noticed rugae among the total study participants primary and secondary. Among the patterns of rugae wavy (92.3%) was most common and significantly more among females. The point (9.8%) type of rugae was the only pattern found to be more in males. It may be concluded that the rugae pattern can be an additional method for post mortem identification in conjunction with the other methods such as visual, fingerprints and dental characteristics in forensic sciences.

Pattern of steroid misuse in vernal keratoconjunctivitis resulting in steroid induced glaucoma and visual disability in Indian rural population: An important public health problem in pediatric age group.

Purpose: To know the pattern of presentations and management outcome of steroid induced glaucoma in vernal keratoconjunctivitis (VKC). Methods: Children of VKC using steroid with two of the following criteria were enrolled: Intraocular pressure (IOP) >21 mm Hg, glaucomatous optic disc and visual field defects. Misused topical steroids were classified in 4 groups; A- Highly potent drugs (dexamethasone, betamethasone), B- Moderate (prednisolone), C- Weak (loteprednol, fluorometholone), D- Unknown drugs. Active/conservative interventions were done to control IOP. Corrected distance visual acuity (CDVA), IOP, anterior segment and fundus examinations were noted. One-way ANOVA test and post hoc Tukey HSD test were used to compare the groups. Results: Out of 1423 VKC patients, 240 were using topical steroid without prescriptions. 92 eyes of 47 patients had steroid induced glaucoma. Hence prevalence of this complication was 3.30% in this study population. Mean age was 14.1 ± 3.8 years. Mean IOP was 38 ± 12 mm of Hg and mean vertical cup disc ratio was 0.67 ± 0.25. IOP was controlled by withdrawal of steroids (9 eyes), with antiglaucoma medications (27), trabeculectomy (57) and glaucoma drainage device (1). Mean CDVA at presentation was better in group C (0.23 log MAR). Mean IOP was highest in group A (43.1 mm Hg) followed by group D (40.5 mm Hg). At presentation 17 were blind (CDVA <3/60). Post treatment marginal improvement in CDVA was found (P = 0.46). However, statistically significantly improvement was noticed in IOP (P < 0.00001). Conclusion: Injudicious use of steroids leads to vision threatening complications like ocular hypertension and glaucoma in children of VKC. Weak steroids like loteprednol or fluorometholone should be used instead of higher potency drugs. Vision and IOP should be monitored fortnightly in children using topical steroids to detect steroid responders at the earliest.

Predominance of unusual rotavirus G1P[6] strain in North India: An evidence from hospitalized children and adult diarrheal patients.

Group A Rotavirus remains the leading cause of gastroenteritis in children and accounts for 0.2 million fatalities each year; out of which, approximately 47,100 deaths occur in India. In adults also, rotavirus is reported to be responsible for diarrhea severe enough to require hospitalizations. India has recently introduced rotavirus vaccine in the Universal Immunization Programme and Himachal Pradesh became the first Indian state to implement this project. This study is an attempt to provide the pre-vaccination data on rotavirus gastroenteritis burden and circulating genotypes in Himachal Pradesh, India. A total of 607 faecal specimens (247 children ≤5years, 50 older children and 310 adults) from hospitalized diarrheal patients from Himachal Pradesh, India were screened for rotavirus using ELISA and RT-PCR. The positive samples were further G/P genotyped using semi-nested PCR. Rotavirus was detected in 25.2% and 28.3% of samples with ELISA and RT-PCR, respectively. In children, rotavirus frequency was significantly high with positivity in 49.0% cases whereas 14.0% adult samples have rotavirus in them. Genotyping of the positive samples revealed predominance of G1 (66.0%) and P[6] (66.7%) genotypes. The most common G and P combination was G1P[6] (62.8%) followed by G1P[8] (16.5%), G9P[6] (7.4%) and G12P[6] (5.0%). Molecular analysis reveals the belonging of P[6] strains in Lineage 1a. This pre-vaccination data on rotavirus prevalence and diversity would be helpful for assessing the affect of vaccination on the disease burden and its comparison with post-vaccination data of circulating genotypes would help in studying the effect on diversity of rotavirus strains possibly due to vaccine selection pressure.

Prevalence of rotavirus, norovirus and enterovirus in diarrheal diseases in Himachal Pradesh, India.

Diarrheal diseases are responsible for a significant proportion of mortality and morbidity all around the globe. The contribution of viruses to gastroenteritis incidences in humans is well established. In the present study, we have studied the prevalence of rotavirus, norovirus and enterovirus in Himachal Pradesh, a north Indian state. A total of 287 (111 children and 176 adults) stool samples of gastroenteritis patients were screened for the viruses using RT-PCR method. 34.5 % samples were positive for the viral pathogens of gastroenteritis. Rotavirus was the predominant virus detected in the study with 49.5 and 14.8 % positivity in children and adults, respectively. Enterovirus was present in 5.6 % cases whereas norovirus had least prevalence (1.4 %). Co infection (rotavirus and enterovirus) was witnessed at the prevalence rate of 0.6 %. Among different age groups, the prevalence of studied viruses was highest in the children belonging to the age groups of <5 years. Rotavirus infections were found to be significantly associated with vomiting and trend of higher rates of fever and dehydration was seen in children along with diarrhea. Seasonal distribution shows circulation of diarrheagenic viruses throughout the year. This is the first report of prevalence of various diarrheagenic viruses circulating in this region. The outcome of the study from this cohort provides a baseline data which can be used to design the preventive strategies in the otherwise unexplored state of Himachal Pradesh.

Oral Health Related Quality of Life in Patients of Head and Neck Cancer Attending Cancer Hospital of Bhopal City, India.

BACKGROUND: To assess the oral health related quality of life (OHRQoL) of head and neck cancer patients and to find association between QoL, demographic and disease variables. METHODS: This cross-sectional study was conducted on 153 patients diagnosed and being treated for head and neck cancer in Jawaharlal Nehru Cancer Hospital, India. Data collected from the survey included demographic details and OHRQoL, which was measured by European Organization of Research for Treatment of Cancer QoL questionnaire head & neck-35. Cancer measurements (location of tumor, stages of cancer, treatment type) were collected from the patient's hospital records. RESULTS: The majority of the population 84 (54.9%) belonged to 41-60 years age group and most of them were male (78.4%). The most frequent site of the primary tumor was the oral cavity (71.3%) and the majority of patients had Stage II and III cancer. Main factors affecting QoL were loss of weight, use of painkillers, sticky saliva, reduced mouth opening and problems in social eating. Significant association found between pain (P = 0.044), swallowing (P = 0.018), sense (P = 0.001), Social eating (P = 0.003), social contact (P = 0.008), reduced mouth opening (P = 0.008) with respect to type of treatment. CONCLUSIONS: We conclude that there was a significant reduction in the QoL in cancer patients resulting from myriad forms of cancers. An assessment of the QoL and symptoms can help the dentist to direct attention to most important symptoms and provide counseling for appropriate interventions towards improving QoL outcomes and the response to the treatment.

Prevalence of Spaced and Non-Spaced Dentition and Occlusal Relationship of Primary Dentition and its Relation to Malocclusion in School Children of Davangere.

BACKGROUND: The aim of the current study was carried to determine the relation of spacing, closed dentition, and occlusal relation with malocclusion in the primary dentition in children during deciduous dentition period among school children of Davangere. MATERIALS AND METHODS: A total of 945 school children all having deciduous teeth were included in the study. Informed consent for the child's participation is taken from the school principal. The dentition was examined under natural daylight, and the data was recorded. All the school children were screened for spaced and non-spaced dentition, molar and canine relationship. RESULTS: The results concluded that most of the children showed spaced dentition (82.1%) when compared to non-spaced dentition (17.9%) with males shown more spaced dentition than compared to females. Among all children examined for molar and canine relation, flush terminal molar relation (65%) showed highest among all molar relation followed by mesial step (31%) and distal step (4%), and Class I canine relation (90%) was significant followed by Class II (6%) and Class III canine relation (4%). No significant difference was seen between right and left side. CONCLUSION: The study concludes that determining the malocclusion and its correction at an early age helps in preventing a future complication in permanent dentition since stable primary occlusion leads to ideal occlusion in permanent dentition. Spacing, i.e., primate and physiologic space with the terminal molar relation in primary dentition indicates proper alignment of the permanent dentition.

Rotaviruses: is their surveillance needed?

Rotaviruses, a major cause of gastroenteritis in children worldwide accounts for around 0.5 million deaths annually. Owing to their segmented genome and frequently evolving capability, these display a wide variation in their genotypes. In addition to commonly circulating genotypes (G1, G2, G3, G4, G9, P[4] and P[8]), a number of infrequent genotypes are being continuously reported to infect humans. These viral strains exhibit variation from one geographical setting to another in their distribution. Though the introduction of vaccines (RotaTeq and Rotarix) proved to be very effective in declining rotavirus associated morbidity and mortality, the number of infections remained same. Unusual genotypes significantly contribute to the rotavirus associated diarrhoeal burden, may reduce the efficacy of the vaccines in use and hence vaccinated individuals may not be benefited. Vaccine introduction may bring about a notable impact on the distribution and prevalence of these viruses due to selection pressure. Moreover, there is a sudden emergence of G2 and G3 in Brazil and United States, respectively, during the years 2006-2008 post-vaccination introduction; G9 and G12 became predominant during the years 1986 through 1998 before the vaccine introduction and now are commonly prevalent strains; and disparity in the predominance of strains after introduction of vaccines and their natural fluctuations poses a vital question on the impact of vaccines on rotavirus strain circulation. This interplay between vaccines and rotavirus strains is yet to be explored, but it certainly enforces the need to continuously monitor these changes in strains prevalence in a particular region. Furthermore, these fluctuations should be considered while administration or development of a vaccine, if rotavirus associated mortality is ever to be controlled.

Total Salivary Anti-oxidant Levels, Dental Development and Oral Health Status in Childhood Obesity.

BACKGROUND: The objectives of this study were to assess the total antioxidant levels, dental development, and oral health status in childhood obesity. MATERIALS AND METHODS: A total of 120 children aged 6-12 years consisting of both genders from different school along Coastal Karnataka, India were part of the study and were categorized into obese/overweight, and normal children based on body mass index for age and sex. Total antioxidant capacity (TAC) levels determined by phosphomolybidic acid and spectrophotometric method were considered. Oral hygiene index-simplified, modified gingival index and dentition status index were used to analyze oral health status. Dental development was assessed using a clinical method and correlated with standard chronology of human dentition. RESULTS: Levels of the total salivary antioxidants were increased in the study group which is very highly significant when compared with control group, oral health status in both the study group and control group was good. Number of children in study group showing accelerated dental development is relatively less when compared with control group, but is not statistically significant. CONCLUSION: Salivary TAC was significantly high in overweight and obese children than their normal counterparts. Prevalence of dental caries was high in obese/overweight children when compared to normal children.

Comparison of different caries diagnostic thresholds under epidemiological and clinical settings among 7-15 year old school children from Bangalore city.

AIM: The aim of this study is to compare the different caries diagnostic thresholds under epidemiological and clinical settings among 7-15 year old school children. MATERIALS AND METHODS: A cross-sectional study was undertaken among 7-15 years old school children of Bangalore city. Total 738 children were enrolled in the study. General information was collected regarding oral hygiene practice and personal habits of the schoolchildren. Subsequently, examination was done under both the settings to record Decayed, missing and filled surfaces index for permanent teeth (DMFS) and Decayed, missing and filled surfaces index for deciduous teeth (dmfs) using the World Health Organization (WHO) and WHO + IL criteria. RESULTS: The present study showed that both the settings (clinical and epidemiological) and diagnostic thresholds (WHO and WHO + IL), could influence the detection of carious lesions. Mean Ds under WHO + Initial lesions (IL) criteria (3.92 + 3.49) was nearly double of WHO criteria (1.88 + 2.73,) and the influence observed was more in 14 years of age, where mean Ds under WHO + IL criteria (5.43 + 2.5) which was more than double of WHO criteria (2.02 + 1.9). CONCLUSION: The choice of a diagnostic threshold (WHO and WHO + IL) and the conditions of examination (epidemiological and clinical) are important for the detection of caries.

Application of photochemical technologies for treatment of landfill leachate.

Because of widely varying practices in solid waste management, an all-inclusive solution to long-term management of landfill leachate is currently not available. There is a major technological need for sustainable, economical options for safe discharge of leachate to the environment. Two potential on-site pretreatment technologies, photochemical iron-mediated aeration (PIMA) and TiO(2) photocatalysis were compared for treatment of landfill leachate at laboratory scale. Results of bench scale testing of real landfill leachate with PIMA and TiO(2) photocatalysis showed up to 86% conversion of refractory COD to complete mineralization, up to 91% removal of lead, up to 71% removal of ammonia without pH adjustment, and up to 90% effective color removal with detention times between 4 and 6h, in field samples. The estimated contact times for 90% removal of COD, ammonia, lead, and color were found to be on the order of 10-200 h for PIMA and 3-37 h for TiO(2) photocatalysis. Testing with actual leachate samples showed 85% TiO(2) photocatalyst recovery efficiency with no loss in performance after multiple (n>4 uses). Pre-filtration was not found to be necessary for effective treatment using either process.

Protein structure prediction aided by geometrical and probabilistic constraints.

Database-assisted ab initio protein structure prediction methods have exhibited considerable promise in the recent past, with several implementations being successful in community-wide experiments (CASP). We have employed combinatorial optimization techniques toward solving the protein structure prediction problem. A Monte Carlo minimization algorithm has been employed on a constrained search space to identify minimum energy configurations. The search space is constrained by using radius of gyration cutoffs, the loop backbone dihedral probability distributions, and various secondary structure packing conformations. Simulations have been carried out on several sequences and 1000 conformations have been initially generated. Of these, 50 best candidates have then been selected as probable conformations. The search for the optimum has been simplified by incorporating various geometrical constraints on secondary structural elements using distance restraint potential functions. The advantages of the reported methodology are its simplicity, and modifiability to include other geometric and probabilistic restraints.