Impact of Using Risk-Based Stratification on Referral of Patients With Chronic Kidney Disease From Primary Care to Specialist Care in the United Kingdom.

INTRODUCTION: The externally validated Kidney Failure Risk Equation (KFRE) for predicting risk of end-stage renal disease (ESRD) has been developed, but its potential impact in a population on referrals for patients with chronic kidney disease (CKD) from primary to specialty nephrology care is not known. METHODS: A cross-sectional population-based study of individuals in United Kingdom primary care registered in The Health Improvement Network database was conducted. National Institute of Health and Care Excellence (NICE) 2014 CKD guidelines versus the 4-variable KFRE set at a >3% risk of ESRD at 5 years were applied to patients identified with CKD stage 3-5 between January 1, 2016, and March 31, 2017. RESULTS: In all, 39,476 (36.6%) of 107,962 adults with CKD stage 3-5 had a urine albumin:creatinine ratio (ACR) available and entered into the primary analysis. Of that, 7566 (19.2%) patients fulfilled NICE criteria for referral, 2386 (31.5%) of whom had a ≤3% 5-year risk of ESRD. Also 8663 (21.9%) patients had a >3% 5-year risk of ESRD, 3483 (40.2%) of whom did not fulfill NICE criteria; this represents 8.8% of the primary population. By using the KFRE threshold rather than NICE criteria for referral, 5869 patients (14.9% of the primary analysis population) would have been reallocated between primary and specialist care. Imputational analysis was used for missing ACR measurements and showed similar results. CONCLUSIONS: A risk-based referral approach would lead to a substantial reallocation of patients between primary care and specialist nephrology care with only a small increase in numbers eligible, ensuring those at higher risk of progression are identified.

Evaluation of Role of Myofibroblasts in Oral Cancer: A Systematic Review.

AIM: To conduct a systematic review on the role of myofibroblasts in progression of oral cancer. The myofibroblast is essential for the integrity of the mammalian body by virtue of its role in wound healing, but it also plays a negative role due to their role in promoting tumor development. SETTINGS AND DESIGN: Systematic review. MATERIALS AND METHODS: Bibliographic searches were conducted in several electronic databases using all publications in PubMed, PubMed central, EMBASE, CancerLit, Google scholar, and Cochrane CCTR between 1990 and June 2015. RESULTS: The search of all publications from various electronic databases revealed 1,371 citations. The total number of studies considered for systematic review was 43. The total number of patients included in the studies was 990. CONCLUSION: Myofibroblasts are a significant component in stroma of oral cancer cases, though not identified in all cases. This systematic review shows that clinical, pathological, and immunohistochemistry tests have correlated the presence of high myofibroblast count in oral cancer cell stroma. KEY MESSAGES: Myofibroblasts play a significant role in oral cancer invasion and progression. Various studies have demonstrated their association with oral cancer. This review tends to highlight their role in the pathogenesis of oral cancer over the decade. HOW TO CITE THIS ARTICLE: Sekhon HK, Sircar K, Kaur G, Marwah M. Evaluation of Role of Myofibroblasts in Oral Cancer: A Systematic Review. Int J Clin Pediatr Dent 2016;9(3):233-239.

Iron absorption in raw and cooked bananas: a field study using stable isotopes in women.

BACKGROUND: Banana is a staple food in many regions with high iron deficiency and may be a potential vehicle for iron fortification. However, iron absorption from bananas is not known. OBJECTIVE: The objective of this study was to evaluate total iron absorption from raw and cooked bananas. DESIGN: Thirty women (34.9±6.6 years) from rural Mexico were randomly assigned to one of two groups each consuming: 1) 480 g/day of raw banana for 6 days, or 2) 500 g/day of cooked banana for 4 days. Iron absorption was measured after extrinsically labeling with 2 mg of (58)Fe and a reference dose of 6 mg (57)Fe; analysis was done using ICP-MS. RESULTS: Iron content in cooked bananas was significantly higher than raw bananas (0.53 mg/100 g bananas vs. 0.33 mg/100 mg bananas, respectively) (p<0.001). Percent iron absorption was significantly higher in raw bananas (49.3±21.3%) compared with cooked banana (33.9±16.2%) (p=0.035). Total amount of iron absorbed from raw and cooked bananas was similar (0.77±0.33 mg vs. 0.86±0.41 mg, respectively). CONCLUSION: Total amount of absorbed iron is similar between cooked and raw bananas. The banana matrix does not affect iron absorption and is therefore a potential effective target for genetic modification for iron biofortification.

Morphological variations of sciatic nerve and piriformis muscle in gluteal region during fetal period

Intramuscular drug injection in the gluteal region is often the most frequent cause of sciatic nerve injury in preterm newborns. Local anatomic variation is one of the predisposing causes of iatrogenic sciatic nerve injury. The aim of this morphological study was to assess the relationship of sciatic nerve with the piriformis muscle and to elucidate variations of fusion of piriformis with neighboring muscles in the gluteal region of Indian human preterm fetuses. Four types of relationship of the sciatic nerve with the piriformis muscle were observed in one hundred gluteal regions of fifty spontaneously aborted, formalin-fixed fetuses, aged 20 to 36 week (24 males and 26 females). In 85% of the gluteal regions, the classic pattern was found, in which the two components of the sciatic nerve fuse with each other proximal to the piriformis, and the fused sciatic nerve emerges at the lower border of the piriformis. In the remaining 15% of the gluteal regions, variations in relationship were found. The most common variation, characterized by the passage of the common peroneal component through the piriformis and the emergence of the tibial part at the lower border of the piriformis, was seen in 9% of the gluteal regions. Common peroneal and tibial components passed above and below the muscle respectively in 3%, and the unsplit sciatic nerve passed through the piriformis in 3% of the gluteal regions. Four types of fusion of the piriformis with the neighboring muscles were seen: namely, no fusion; fusion with superior gamellus; fusion with gluteus medius, or fusion with gluteus medius and obturator internus complex in 28%, 43%, 26% and 3% of the gluteal regions respectively. Anatomical variations of the sciatic nerve in relation to the piriformis muscle should be kept in mind while performing medical or surgical interventions in this region

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Anatomical survey of terminal branching patterns of superficial branch of radial nerve in fetuses.

BACKGROUND: Regional anesthesia plays a key role in elective as well as emergency orthopedic and other surgeries in children. However, peripheral nerve blocks are quite challenging in children due to lack of precise anatomical knowledge of the course and distribution of these nerves. The purpose of this study was to explore the terminal branches of the superficial branch of the radial nerve in fetuses. The relationship of the superficial branch of the radial nerve with cephalic vein and surrounding tendons was also observed. METHODS: A total of 60 upper extremities (42 males and 18 females) of 30 spontaneously aborted fetuses (32-40 weeks) were dissected to expose the superficial branch of the radial nerve in the distal forearm and hand. RESULTS: Three patterns of distribution based on the total area of the dorsum of the hand innervated were observed. Type 1 (66.7%): superficial branch of radial nerve (SBRN) innervated lateral two-and-a-half digits; Type 2 (23.3%): SBRN innervated lateral three digits; Type 3 (10%): SBRN innervated lateral three-and-a-half digits. The cephalic vein was seen to intersect the nerve more than twice along its course. CONCLUSIONS: Detailed knowledge of the distribution patterns of terminal branches of superficial branch of radial nerve in hand will enhance the success rate of regional blocks or hand surgeries and minimize the postoperative complications due to injury to nerve or vascular structures.

Apoptosis-related genes confer resistance to Fusarium wilt in transgenic 'Lady Finger' bananas.

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most devastating diseases of banana (Musa spp.). Apart from resistant cultivars, there are no effective control measures for the disease. We investigated whether the transgenic expression of apoptosis-inhibition-related genes in banana could be used to confer disease resistance. Embryogenic cell suspensions of the banana cultivar, 'Lady Finger', were stably transformed with animal genes that negatively regulate apoptosis, namely Bcl-xL, Ced-9 and Bcl-2 3' UTR, and independently transformed plant lines were regenerated for testing. Following a 12-week exposure to Foc race 1 in small-plant glasshouse bioassays, seven transgenic lines (2 × Bcl-xL, 3 × Ced-9 and 2 × Bcl-2 3' UTR) showed significantly less internal and external disease symptoms than the wild-type susceptible 'Lady Finger' banana plants used as positive controls. Of these, one Bcl-2 3' UTR line showed resistance that was equivalent to that of wild-type Cavendish bananas that were included as resistant negative controls. Further, the resistance of this line continued for 23-week postinoculation at which time the experiment was terminated. Using TUNEL assays, Foc race 1 was shown to induce apoptosis-like features in the roots of wild-type 'Lady Finger' plants consistent with a necrotrophic phase in the life cycle of this pathogen. This was further supported by the observed reduction in these effects in the roots of the resistant Bcl-2 3' UTR-transgenic line. This is the first report on the generation of transgenic banana plants with resistance to Fusarium wilt.

Anatomical variation in formation of brachial plexus and its branching.

Variant brachial plexus formation with two trunks and two cords is uncommon and has clinical implications as it may result in failure of regional brachial or axillary block. During routine anatomical dissection, unilateral variation in the formation of brachial plexus accompanied by unusual positional relationship with axillary artery was discovered in the left upper extremity of a 52-year-old Indian male cadaver. Brachial plexus showed two trunks formed by ventral rami of C5, C6 and C7, C8, T1 spinal nerves, respectively, which first split and then reunited in an unusual manner to form two cords: posterior and lateral instead of three. Medial cord was absent. The branching pattern of the brachial plexus also showed important variations. Second part of axillary artery was found lying inferomedial to brachial plexus instead of passing between medial and lateral cords. Transverse cervical artery was found to be coursing between two trunks instead of passing superficial to brachial plexus. Median nerve was observed to be formed from a single root, instead of usual two roots. Embryologically, this rare variation may be due to the development of axillary artery from ninth segmental artery instead of usual seventh cervical intersegmental artery. Such rare variation is clinically important as this knowledge may help the anesthesiologists and the surgeons to avoid any inadvertent damage to nerves and axillary artery during blocks and surgical interventions.

Surgical anatomy of sensory portion of superficial fibular nerve for harvesting nerve grafts from fetuses.

The use of superficial fibular nerve (Sfn) as a potential donor nerve in nerve grafting has been introduced. The limited availability of donor nerves has paved the way for nerve allografting. We studied the sensory portion of Sfn in 60 limbs from 30 fetuses. Three distinct patterns of the nerve were designated as Types 1, 2, and 3 by us. Type 1 (66.67%) comprised Sfn piercing fascia cruris then branching into Mdn and Idn. Type 2 (21.67%) was a pattern where Sfn penetrated deep fascia then continued undivided over the dorsum of foot. Type 3 (11.67%) was where Mdn and Idn penetrated deep fascia independently. The study provided quantitative measurement data of the sensory portion of Sfn and its branching nerves with respect to osseous landmarks like the head of fibula and the malleoli. Such data may be of help in defining nerve segments suitable for harvesting in nerve grafts from fetuses.

Anatomical dimensions of larynx, epiglottis and cricoid cartilage in foetuses and their relationship with crown rump length.

BACKGROUND: Advances in perinatal care and increased use of diagnostic and interventional procedures on foetal airway demand a clear understanding of their normal anatomy and development. This study is aimed at determining the normal dimensions of larynx, cricoid cartilage and epiglottis and their correlation to age and crown rump length (CRL). METHOD: After approval from institutional ethics committee and written parental informed consent, laryngeal measurements were taken from 79 foetuses of varying CRL from 30 to 299 mm. The entire larynx from the tip of epiglottis to lowest extension of thyroid gland was isolated and preserved. In small foetuses (30-165 mm) the measurements were taken under a dissecting microscope. In foetuses above the CRL of 165 mm, the measurements were taken with help of Vernier Calliper. RESULTS: Foetuses were analysed for dimensions based on CRL. The length of the larynx significantly increased in comparison to CRL (P < 0.001). Similar measurements were observed for transverse diameter, anteroposterior diameter and inter-cartilaginous distance of larynx, the anterior height of arch and posterior height of lamina of cricoid cartilage and the length and breadth of epiglottis. The internal anteroposterior and transverse diameter of cricoid cartilage showed no correlation with CRL. CONCLUSION: All the measured parameters of larynx, epiglottis and cricoid cartilage showed positive correlation with the CRL except the internal diameters of cricoid.

Bilateral multiple complex variations in the formation and branching pattern of brachial plexus.

Bilateral variations in the formation and branching of brachial plexus are extremely rare. Multiple bilateral variations in brachial plexus right from divisions to branching pattern were observed during the dissection in an adult male cadaver. Lateral and medial cord formation showed deviation from the usual pattern. Anterior division of upper trunk continued as lateral cord. Medial cord was formed by the union of anterior division of lower trunk and anterior division of middle trunk, thus receiving fibers from both the trunks. Anterior division of middle trunk bifurcated into upper and lower branches. We encountered two lateral roots bilaterally and two medial roots of median nerve on the left side with anomalous origin. There were three upper subscapular nerves on the left and two on the right side with variations in their origin. Anomalous origin of many other branches on both sides was encountered. It is extremely uncommon to find so many variations in one body and bilateral variations are still too rare. Understanding of such variations is clinically important for diagnosing unexplained clinical signs and symptoms as well as during nerve blocks and certain surgical procedures around the neck and proximal arm.

Inhibition of Agrobacterium-induced cell death by antiapoptotic gene expression leads to very high transformation efficiency of banana.

The death of plant cells in culture following exposure to Agrobacterium tumefaciens remains a major obstacle in developing Agrobacterium-mediated transformation into a highly efficient genotype-independent technology. Here, we present evidence that A. tumefaciens exposure induces cell death in banana cell suspensions. More than 90% of embryogenic banana cells died after exposure to A. tumefaciens and cell death was accompanied by a subset of features associated with apoptosis in mammalian cells, including DNA laddering, fragmentation, and formation of apoptotic-like bodies. Importantly, these cellular responses were inhibited in cells expressing the animal antiapoptosis genes Bcl-xL, Bcl-2 3' untranslated region, and CED-9. Inhibition of cell death resulted in up to 90% of cell clumps transformed with Bcl-xL, a 100-fold enhancement over vector controls, approaching the transformation and regeneration of every "transformable" cell. Similar results using sugarcane, a crop plant known for recalcitrance to Agrobacterium transformation, suggest that antiapoptosis genes may inhibit these phenomena and increase the transformation frequency of many recalcitrant plant species, including the major monocot cereal crop plants. Evidence of inhibition of plant cell death by cross-kingdom antiapoptotic genes also contributes to the growing evidence that genes for control of programmed cell death are conserved across wide evolutionary distances, even though these mechanisms are not well understood in plants.

Targeted expression of redesigned and codon optimised synthetic gene leads to recrystallisation inhibition and reduced electrolyte leakage in spring wheat at sub-zero temperatures.

Antifreeze proteins (AFPs) adsorb to ice crystals and inhibit their growth, leading to non-colligative freezing point depression. Crops like spring wheat, that are highly susceptible to frost damage, can potentially be made frost tolerant by expressing AFPs in the cytoplasm and apoplast where ice recrystallisation leads to cellular damage. The protein sequence for HPLC-6 alpha-helical antifreeze protein from winter flounder was rationally redesigned after removing the prosequences in the native protein. Wheat nuclear gene preferred amino acid codons were used to synthesize a recombinant antifreeze gene, rAFPI. Antifreeze protein was targeted to the apoplast using a Murine leader peptide sequence from the mAb24 light chain or retained in the endoplasmic reticulum using C-terminus KDEL sequence. The coding sequences were placed downstream of the rice Actin promoter and Actin-1 intron and upstream of the nopaline synthase terminator in the plant expression vectors. Transgenic wheat lines were generated through micro projectile bombardment of immature embryos of spring wheat cultivar Seri 82. Levels of antifreeze protein in the transgenic lines without any targeting peptide were low (0.06-0.07%). The apoplast-targeted protein reached a level of 1.61% of total soluble protein, 90% of which was present in the apoplast. ER-retained protein accumulated in the cells at levels up to 0.65% of total soluble proteins. Transgenic wheat line T-8 with apoplast-targeted antifreeze protein exhibited the highest levels of antifreeze activity and provided significant freezing protection even at temperatures as low as -7 degrees C.

Cloning and pharmacological characterization of the cat urotensin-II receptor (UT).

Urotensin-II (U-II), acting through its G-protein-coupled receptor, UT, is a possible contributor to hypertension. Variable functional responses to U-II, both within and between species studied to date, complicate the characterization of UT antagonists. In the cat, however, U-II causes systemic hypertension and constricts arterial segments isolated from several vascular beds. The purpose of this study was to clone and pharmacologically characterize cat recombinant UT to determine whether this system represents a model for characterizing UT antagonists. Cloned cat UT displayed 74% identity to primate UT, and 77% identity to rodent UT. [(125)I] hU-II bound in a saturable manner to a single site on recombinant cat UT with high affinity (K(D) 288+/-13pM) and high density (B(max) 747+/-66fmol/mg protein). U-II isopeptides displayed equipotent, high affinity binding to cat UT (K(i) 1.8-5.3nM). Cat UT was coupled to intracellular [Ca(2+)] release (EC(50) 0.6+/-0.2nM) and total inositol phosphate (IP) formation (EC(50) 0.4+/-0.1nM). Protein kinase C activation desensitized cat, but not human, UT-mediated IP formation. UT mRNA expression was detected in cat blood vessels, trachea, lung, and kidney, where the medulla (K(D) 815+/-34) and cortex and (K(D) 316+/-39pM) displayed high affinity binding for human U-II (hU-II). The cat urotensin-II receptor represents a suitable in vitro model to examine the role of the U-II/UT system in the etiology of hypertension, assisting in the evaluation of the UT antagonists to help treat cardiovascular disease.