The BRCA mutation spectrum among breast and ovarian cancers in India: highlighting the need to screen BRCA1 185delAG among South Indians.

Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers. We also aimed to identify population specific BRCA1/2 mutation hotspots, to enable the development of more affordable testing strategies. We identified 921 patients with breast and ovarian cancer who underwent mutation testing. The target enrichment was followed by targeted NGS in 772 patients and an allele-specific PCR (ASPCR) based genotyping for BRCA1:c.68_69delAG (or 185delAG), was carried out in 149 patients. We identified 188 (20.4%) patients with BRCA1/2 variants: 118 (62.8%) with pathogenic/likely pathogenic and 70 (37.2%) with VUS. The 185delAG was identified as a recurrent mutation in the Southern Indian population, accounting for 24.6% of the pathogenic variants. In addition, a family history of breast, ovary, pancreas, or prostate (BOPP) cancer was found to be associated with an increased risk of identifying a deleterious BRCA1/2 variant [OR = 2.11 (95% CI 1.45-3.07) p ≤ 0.001]. These results suggest that Targeted NGS is a sensitive and specific strategy for BRCA testing. For Southern Indian patients, a two-tiered approach can be considered: Initial screening with ASPCR for BRCA1 185delAG followed by NGS for those testing negative. Expanding the gene panel and identifying other population-specific mutation hot spots is a promising area with potential for improvements in testing and treatment strategies.

A rare case of schwannomatosis with meningioma: a case report.

Introduction: Schwannomatosis is characterized by multiple schwannomas without vestibular schwannomas or any other stigmata of neurofibromatosis type 2 (NF2). Schwannomatosis is a rare disorder, with a reported incidence ranging from 1 in 40 000 to 1 in 1.7 million. Meningioma is also associated with schwannomatosis in around 5% of cases. Case presentation: We describe a case of a 20-year-old female presenting with progressive weakness of the right lower limb for 7 months with a tingling sensation and numbness of the same limb for 6 months and was found to have schwannomatosis with multiple spinal and right cerebellopontine angle (CPA) (9th/10th cranial nerve) schwannomas and left anterior cranial fossa meningioma. Discussion: Schwannomas in schwannomatosis are seen along the cranial, spinal, and peripheral nerves but not along the vestibular nerve, as is characteristically seen in NF2. The occurrence of meningiomas is about 5% in individuals with schwannomatosis, and the patient in our case also had an associated meningioma. The tumor was confirmed to be a schwannoma based on features on an MRI examination and histological examination. Conclusion: It is of great significance to identify the entire spectrum of the disease in a patient with schwannomatosis, and to differentiate it from related conditions in order to track and surgically manage the patient appropriately based on symptomatology and imaging findings.

A Quantitative Assessment to Compare the Dimensions of the Alveolar Ridge Width Using Different Techniques for Implant Placement.

BACKGROUND: The success of any dental implant surgery depends on the correct diagnosis and treatment planning. PURPOSE: The aim of this study was to compare the dimensions of the alveolar ridge width using different techniques for implant placement. MATERIALS AND METHODS: The study involved 27 partially edentulous subjects aged 18-50, including males and females. In this study, the dimensions of the ridge were evaluated by ridge mapping on a cast, ridge mapping using a bone caliper, and ridge mapping with the help of an occlusal radiograph. All three methods were compared with ridge mapping by cone beam computed tomography (CBCT). For each subject, the site of implant placement was marked on the study model. Alveolar ridge measurement was done in the mouth by a bone caliper under local anesthesia with the help of a stent with a hole. Ridge mapping on a cast was done after sectioning the cast and marking with the help of a periodontal probe and stent. Ridge mapping was done on an occlusal radiograph by converting an acetate stent into a radiographic stent. Finally, CBCT was taken for each patient for ridge mapping. All four readings were tabulated. RESULTS: Comparing the mean alveolar ridge width of four groups, ANOVA showed significantly different alveolar ridge width among the groups (F=7.89, p<0.001). The validity (accuracy and precision) of ridge mapping on a cast, ridge mapping using a bone caliper, and occlusal radiograph against the CBCT (gold standard) was done using concordance correlation analysis. The concordance correlation analysis showed the highest association (ρ=0.8196) and precision (ϸ=82.61%) of ridge mapping using a bone caliper with CBCT. However, the accuracy of ridge mapping on a cast (Cb=99.42%) was the highest, followed by ridge mapping using a bone caliper (Cb=82.61%). The analysis concluded that both techniques are equivalent to CBCT and can be used interchangeably. CONCLUSION: The mean alveolar ridge width of the occlusal radiograph was the highest, followed by CBCT, ridge mapping on a cast, and ridge mapping using a bone caliper the least (occlusal radiograph > CBCT > ridge mapping on cast >ridge mapping using bone caliper). But at the same time, it can also be used interchangeably.

Delayed presentation of traumatic diaphragmatic hernia complicated by bowel obstruction and perforation: a case report.

Post-traumatic diaphragmatic hernia is a rare but life-threatening condition resulting from a traumatic injury to the diaphragm. We present a case of a 48-year-old man with a history of fall injury and a delayed presentation of a right-sided diaphragmatic hernia with subsequent bowel obstruction and perforation in a patient with a history of trauma and tuberculosis. The patient underwent exploratory laparotomy with manual reduction of the herniated bowel, primary repair of the diaphragmatic defect, and the creation of a double-barrel ileostomy. This case highlights the importance of considering traumatic diaphragmatic hernia in patients with a history of trauma presenting with abdominal symptoms. Timely diagnosis and surgical intervention are crucial in preventing serious complications associated with this condition.

Visual processing and collective motion-related decision-making in desert locusts.

Collectively moving groups of animals rely on the decision-making of locally interacting individuals in order to maintain swarm cohesion. However, the complex and noisy visual environment poses a major challenge to the extraction and processing of relevant information. We addressed this challenge by studying swarming-related decision-making in desert locust last-instar nymphs. Controlled visual stimuli, in the form of random dot kinematograms, were presented to tethered locust nymphs in a trackball set-up, while monitoring movement trajectory and walking parameters. In a complementary set of experiments, the neurophysiological basis of the observed behavioural responses was explored. Our results suggest that locusts use filtering and discrimination upon encountering multiple stimuli simultaneously. Specifically, we show that locusts are sensitive to differences in speed at the individual conspecific level, and to movement coherence at the group level, and may use these to filter out non-relevant stimuli. The locusts also discriminate and assign different weights to different stimuli, with an observed interactive effect of stimulus size, relative abundance and motion direction. Our findings provide insights into the cognitive abilities of locusts in the domain of decision-making and visual-based collective motion, and support locusts as a model for investigating sensory-motor integration and motion-related decision-making in the intricate swarm environment.

Progress in Diagnosis and Treatment of Neonatal Sepsis: A Review Article.

Neonatal sepsis is a serious condition in which the pathogens infiltrate the bloodstream, multiply and produce toxins causing deleterious effects to the health of neonates. It is divided into two types on the basis of the time of onset. Early onset sepsis occurs within 72 hours of birth and late onset sepsis begins after 72 hours of delivery. Neonatal sepsis continues to be a common and significant health care burden, especially in very low birth weight infants (with birthweight less than 1500 grams). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remain a challenge. Keywords: cytokines; immunoglobulin; neonatal sepsis; procalcitonin.

Intercomparison of model predictions of 14C concentrations in agricultural plants following acute exposures to airborne 14C.

Carbon-14 (14C) is one of the main radionuclides released during normal operation by nuclear power plants, nuclear defense facilities and nuclear fuel reprocessing plants. It is mainly released in the form of carbon dioxide gas denoted 14CO2, which has the specificity of being incorporated into food webs via photosynthesis by primary producing organisms. In order to better assess the environmental and human impacts of 14CO2 under normal operating conditions - or after potential accidental releases - from nuclear facilities, it is necessary to improve our understanding and our predictions of the behaviour of this radionuclide along the human food chain. To achieve this goal, the International Atomic Energy Agency (IAEA) Environmental Modelling for Radiation Safety (EMRAS) model evaluation programme included the Tritium and 14C Working Group (TCWG) which dealt with the intercomparison exercises between several models of environmental transfer in the case of routine and accidental releases of these radionuclides into the environment, and their performance testing. The TOCATTA-χ model developed at IRSN is a dynamic compartment model with high temporal resolution, which simulates the transfer of 14C (and tritium) in grassland ecosystems exposed to gaseous 14CO2 (and HTO) from nuclear facilities under normal or accidental operating conditions. Following this work, IRSN proposed a related project to extend the application of the TOCATTA-χ model to 14C estimates in leafy vegetables, fruits and roots. This article deals with the application of the TOCATTA-χ model to a specific real-case scenario identified within the framework of the TCWG. The scenario provides experimental data and predicted results from models developed at the international level. Model-model and model-data intercomparison exercises were thus carried out to validate the evaluations of the TOCATTA-χ model. In addition, this paper discusses the parameterization of the TOCATTA-χ model for this scenario and the development of modules for 14C concentrations in potato tubers, based on the assumption that photosynthetic transfer occurs directly from leaves to tubers and depends mainly on the growth stage of the tubers. It is observed that the predictions of the TOCATTA-χ model for the concentrations of 14C in leaves and tubers are slightly better than the other models due to the modelling approaches adopted by TOCATTA-χ for the calculation of key ecophysiological processes that govern plant functioning. Overall, the TOCATTA-χ model reduces the Root Mean Square Error (RMSE) by a factor of less than 8 compared to other models. In addition, most of the predicted results of the TOCATTA-χ model better match the measurements and are within the measurement uncertainty limit, while a few are overestimated. This could be due to the high uncertainty associated with the experimentally measured 14C activities, which reflects the field variability in plant growth rate.

Chemistry and biological evaluation of pyrido[4,3-d]pyrimidines: A review.

The aim of this review is to update the knowledge of different multi-component reactions that lead to synthesizing of pyrido[4,3-d]pyrimidines. In this study, the multiple synthetic pathways that are discussed in the synthesis of pyrido[4,3-d]pyrimidines lead are highlighted. Thus, the developed compounds have been derived from pyridine and pyrimidines fusion or from possible approaches of multistep synthesis reaction versatility. Apart from the synthetic schemes, their biological applications are also comprehended. This review discusses that the pyrido[4,3-d]pyrimidines have been developed by using new strategies and may be useful to future researchers.

Sustainable adsorptive removal of antibiotics from aqueous streams using Fe3O4-functionalized MIL101(Fe) chitosan composite beads.

In this study, we synthesized recyclable Fe3O4-functionalized MIL101(Fe) chitosan composite beads for the removal of tetracycline (TC), doxycycline (DC) and ciprofloxacin (CFX) antibiotics from aqueous streams. More than 99% removal efficiency for each antibiotic was achieved at optimum pH, dosage, concentration and contact time. Langmuir adsorption isotherms and pseudo-second-ord er kinetic model were suitable with correlation coefficient values close to 1 for all the antibiotics. Adsorption capacities of 45.33, 33.20 and 31.30 mg g-1 for TC, DC and CFX, respectively, were reported by the synthesized Fe3O4-functionalized MIL101(Fe) chitosan composite beads. The Fe3O4-functionalized MIL101(Fe) chitosan composite beads were also tested for their regeneration ability, and a remarkable regeneration ability over up to 5 cycles was observed. The adsorption of TC, DC and CFX on the surface of Fe3O4-functionalized MIL101(Fe) chitosan composite beads was governed by the π-π interaction, H-bonding and electrostatic interaction between the antibiotics and adsorbent due to protonation, deprotonation and cation exchange in the aqueous solution. These results showed a good prospect for applying the reported beads towards removing antibiotics from pharmaceutical industry wastewater.

Status Dystonicus with Atypical Presentation in Developmentally Delay Child: A Case Report.

Status dystonicus is characterised by involuntary sustained or intermittent muscle contractions of muscles causing repetitive twisting movements, abnormal postures of the body, or both is a rare but life-threatening movement disorder. Early diagnosis and management of status dystonicus prevent serious complications. We report a 2 years old previously developmental delay diagnosed girl who presented with generalised contractions of the whole body. Tightening of limbs is aggravated by touching her backside which is a very unique feature. Dystonia is associated with severe sweating and was confused with a seizure event. The patient was treated with midazolam, clonidine, phenytoin, gabapentin, pyridoxine, baclofen, and trihexyphenidyl. She was admitted to the intensive care unit for monitoring. The patient partially recovered after 10 days of treatment. Keywords: aspiration; children; dystonia; epilepsy; pneumonia.

Polarization vision in invertebrates: beyond the boundaries of navigation.

Invertebrates possess the unique ability to see polarized light. This allows them to exploit the rich polarization information embedded in their natural environments: patterns in plants, high contrast on water surfaces, distinctive signatures of conspecifics, and the celestial polarization pattern around the sun. From this wide repertoire of polarization signals, studies have primarily focused on understanding how celestial polarization information is converted into an internal compass. This review highlights several studies which suggest that spatio-temporal polarization information is utilized by insects for additional functions, such as signaling, detection, contrast enhancement, and host assessment. It concludes by evaluating recent technological advances for uncovering the full repertoire of polarization-sensitivity in invertebrates.

Quinolines, a perpetual, multipurpose scaffold in medicinal chemistry.

Quinoline is a versatile pharmacophore, a privileged scaffold and an outstanding fused heterocyclic compound with a wide range of pharmacological prospective such as anticancer, anti-inflammatory, antibacterial, antiviral drug and superlative moiety in drug discovery. The quinoline hybrids have already been shown excellent results with new targets with a different mode of actions as an inhibitor of cell proliferation by cell cycle arrest, apoptosis, angiogenesis, disruption of cell migration and modulation. This review emphasized the mode of action, structure activity relationship and molecular docking to reveal the various active pharmacophores of quinoline hybrids accountable for novel anticancer, anti-inflammatory, antibacterial and miscellaneous activities. Therefore, several quinoline candidates are under clinical trials for the treatment of certain diseases, for example ferroquine (antimalarial), dactolisib (antitumor) and pelitinib (EGFR TK inhibitors) etc. Plenty of research has been summarized the recent advances of quinoline derivatives and explore the various therapeutic prospects of this moiety. This review would help the researchers to strategically design diverse novel quinoline derivatives for the development of clinically viable drug candidates for the treatment of incurable diseases.

An overview on synthetic and pharmaceutical prospective of pyrido[2,3-d]pyrimidines scaffold.

Pyrido[2,3-d]pyrimidine, a fused hetero-bicyclic nucleus containing pyridine and pyrimidine rings has attained the momentary attention in the sphere of multicomponent synthetic protocol and medicinal chemist. Pyrido[2,3-d]pyrimidine derived drugs have manifested diverse pharmacological activities, particularly, anti-inflammatory, cytotoxic, antimicrobial, phosphodiesterase inhibitors and cytokine inhibitors etc. The present review illustrates various modern synthetic strategies adopted, the structure-activity relationship (SAR) aspects and discloses the extensive crucial biological properties (anticancer, anti-infectious, anti-diabetics and CNS agents) of pyrido[2,3-d]pyrimidines.

"ASURE": A multi-potential plant bioassay as a pre-determinative microbial efficiency testing tool for bioinoculant studies.

Bioinoculant studies focusing on plant-microbe association hold immense importance for research in field of agriculture and plant science. Such plant-microbe associations are amongst the most complex and beneficial partnerships in nature. Research focused to explore favourable host-microbe relationship requires a contamination free, non-interceptive and easily manageable system where these interactions can be studied in real-time. Also a provision for efficient sample recovery to support a variety of analyses would be a definite advantage. The manuscript proposes a new multi-potential plant bioassay abbreviated "ASURE" inspired by hydroponics. ASURE is a robust system, providing a workable solution to challenges faced during in-vitro microcosm studies. Significance of this system is its plant growth supporting design, facilitating comparative assessment of PGPM treatment benefits to host plant while providing a closer real-time view of plant microbe association. •ASURE serves as a testing tool to pre-determine the efficiency of various plant friendly microbes to develop them as future bioinoculants.•ASURE accommodates 16 individual samples in a 12 × 12 cm space, ensures homogenous micro environment and facilitates continuous and undisturbed (real-time) monitoring of root and shoot growth.•ASURE enables efficient sample recovery with zero loss during harvesting and no interception from substrate.

Role of Musa paradisiaca ascorbate peroxidase in the transformation of methyl phenyl sulfide to its sulfoxide.

An ascorbate peroxidase from a new source Musa paradisiaca leaf juice has been purified to homogeneity using a simple procedure involving concentration by ultra filtration and anion exchange chromatography on diethyl amino ethyl [DEAE] cellulose column. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis [SDS-PAGE] analysis of the purified enzyme has shown a single protein band of molecular mass 208.9 kDa which has been confirmed by native-PAGE and intact mass analysis by mass spectrometry. The Km and kcat values of the enzyme using ascorbate and H2O2 as the variable substrates were 0.13 m mol L-1, 40.42 s-1 and 0.23 m mol L-1, 27.24 s-1, respectively. The pH and temperature optima of the enzyme were 7.0 and 298 K, respectively. The enzyme transformed approximately 97% methyl phenyl sulfide to its sulfoxide. The product was racemic mixture.

History Matters: Oviposition Resource Acceptance in an Exploiter of a Nursery Pollination Mutualism.

In the fig-fig wasp nursery pollination system, parasitic wasps, such as gallers and parasitoids that oviposit from the exterior into the fig syconium (globular, enclosed inflorescence) are expected to use a variety of chemical cues for successful location of their hidden hosts. Behavioral assays were performed with freshly eclosed naive galler wasps. Syconia with different oviposition histories, i.e. with or without prior oviposition, were presented to wasps in no-choice assays and the time taken to the first oviposition attempt was recorded. The wasps exhibited a preference for syconia previously exposed to conspecifics for oviposition over unexposed syconia. Additionally, syconia exposed to oviposition by heterospecific wasps were also preferred for oviposition over unexposed syconia indicating that wasps recognise and respond to interspecific cues. Wasps also aggregated for oviposition on syconia previously exposed to oviposition by conspecifics. We investigated chemical cues that wasps may employ in accepting an oviposition resource by analyzing syconial volatile profiles, chemical footprints left by wasps on syconia, and syconial surface hydrocarbons. The volatile profile of a syconium is influenced by the identity of wasps developing within and may be used to identify suitable host syconia at long range whereas close range preference seems to exploit wasp footprints that alter syconium surface hydrocarbon profiles. These cues act as indicators of the oviposition history of the syconium, thereby helping wasps in their oviposition decisions.

The insect ovipositor as a volatile sensor within a closed microcosm.

We show that the insect ovipositor is an olfactory organ that responds to volatiles and CO2 in gaseous form. We demonstrate this phenomenon in parasitic wasps associated with Ficus racemosa where ovipositors, as slender as a human hair, drill through the syconium (enclosed inflorescences) and act as a guiding probe to locate highly specific egg-laying sites hidden inside. We hypothesize that olfaction will occur in the ovipositors of insects such as parasitic fig wasps where the hosts are concealed and volatile concentrations can build up locally. Relevant stimuli such as herbivore-induced fig volatiles and CO2 elicited electrophysiological responses from the ovipositors. Silver nitrate staining also revealed pores in ovipositor sensilla, indicating their olfactory nature. Insects could use volatile sensors on their ovipositors to evaluate ecologically relevant stimuli for oviposition. Further investigations on the sensory nature of ovipositors can provide designs for development of ovipositor-inspired micro-chemosensors.

Effect of incorporation of silane-treated silver and aluminum microparticles on strength and thermal conductivity of PMMA.

PURPOSE: The purpose of this study was to study the effect of addition of metal filler particles on different strengths of polymethylmethacrylate (PMMA) and to evaluate the thermal perception in vivo. MATERIALS AND METHODS: The study was carried out in two parts. Part 1 of the study was an in vitro investigation regarding the effect of addition of metal fillers (aluminum and silver) in concentrations of 10%, 20%, and 30%, by volume on the tensile, compressive, and flexural strength of PMMA. Part 2 of the study comprised the clinical evaluation of the thermal perception by 10 edentulous patients provided with two sets of complete dentures, one fabricated with unfilled PMMA and another with 20% aluminum particle filled PMMA on the palatal portion of the maxillary denture. Recorded data were subjected to Student's t-test and ANOVA test. RESULTS: The mean tensile and flexural strength values among control and other groups were found to have statistically significant differences (p < 0.05) except for Al1 and Al2 groups. Mean compressive strength values among control and other groups were statistically significant (p < 0.05). In the clinical study, all 10 participants reported higher perception of hot and cold sensations in dentures with a metalized palatal portion. CONCLUSIONS: Compressive strength increased progressively on increasing the filler concentration for both silver- and aluminum-filled PMMA. Silane-treated metalized PMMA showed reduction in tensile and flexural strength at 30% concentration. Metalized dentures led to an appreciable increase in thermal perception by the participants of this study.

Purification and characterization of Mn-peroxidase from Musa paradisiaca (banana) stem juice.

Mn-peroxidase (MnP), a biotechnologically important enzyme was purified for the first time from a plant source Musa paradisiaca (banana) stem, which is an agro-waste easily available after harvest of banana fruits. MnP was earlier purified only from the fungal sources. The enzyme was purified from stem juice by ultrafiltration and anion-exchange column chromatography on diethylamino ethylcellulose with 8-fold purification and purification yield of 65%. The enzyme gave a single protein band in SDS-PAGE corresponding to molecular mass 43 kDa. The Native-PAGE of the enzyme also gave a single protein band, confirming the purity of the enzyme. The UV/VIS spectrum of the purified enzyme differed from the other heme peroxidases, as the Soret band was shifted towards lower wavelength and the enzyme had an intense absorption band around 250 nm. The K(m) values using MnSO4 and H2O2 as the substrates of the purified enzyme were 21.0 and 9.5 microM, respectively. The calculated k(cat) value of the purified enzyme using Mn(II) as the substrate in 50 mM lactate buffer (pH 4.5) at 25 degrees C was 6.7s(-1), giving a k(cat)/K(m) value of 0.32 microM(-1)s(-1). The k(cat) value for the MnP-catalyzed reaction was found to be dependent of the Mn(III) chelator molecules malonate, lactate and oxalate, indicating that the enzyme oxidized chelated Mn(II) to Mn(III). The pH and temperature optima of the enzyme were 4.5 and 25 degrees C, respectively. The enzyme in combination with H2O2 liberated bromine and iodine in presence of KBr and KI respectively. All these enzymatic characteristics were similar to those of fungal MnP. The enzyme has the potential as a green brominating and iodinating agent in combination with KBr/KI and H2O2.