Common cloaca: An uncommon entity posing diagnostic and management challenges: Our experience with nine cases.

BACKGROUND: Cloacal anomalies are the severest and most complex of all anorectal malformations (ARMs). They require careful evaluation and meticulous surgery tailored to suit each variant. We present our experience in a series of nine cases. METHODS: This includes a retrospective review of 9 cases of cloaca managed at a tertiary care centre between 2015 and 2019. RESULTS: Associated anomalies were seen in 44% cases. The definitive surgery was performed at a mean age of 15.2 months (10 months-19 months), the definitive surgery being rectal separation with total urogenital mobilisation. The common channel as measured during panendoscopy was up to 3 cm in 7 patients (78%), and only 2 patients had a common channel of more than 3 cm (22%). Of the 34 procedures that these nine patients underwent, there were four complications (12%). The median follow-up period after stoma closure was 18 months (5-32 months), and the mean age at last follow-up was 38 months (22-48 months). Five children (63%) had spontaneous voiding and remained dry in the intervening period. Three patients (37%) had poor urinary stream with dribbling and high postvoid residue requiring clean intermittent catheterisation. Six patients had faecal soiling (66%); four had daily soiling; and two had occasional soiling. Four patients had constipation (44%). Seven patients (77%) required daily enemas for bowel evacuation and to remain dry. CONCLUSION: Cloacal anomalies are rare and complex ARMs. Satisfactory urinary and bowel continence rates can be achieved even in these complex anomalies.

Publisher Correction: Impact of alloy fluctuations and Coulomb effects on the electronic and optical properties of c-plane GaN/AlGaN quantum wells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Impact of alloy fluctuations and Coulomb effects on the electronic and optical properties of c-plane GaN/AlGaN quantum wells.

We report on a combined theoretical and experimental study of the impact of alloy fluctuations and Coulomb effects on the electronic and optical properties of [Formula: see text]-plane GaN/AlGaN multi-quantum well systems. The presence of carrier localization effects in this system was demonstrated by experimental observations, such as the "S-shape" temperature dependence of the photoluminescence (PL) peak energy, and non-exponential PL decay curves that varied across the PL spectra at 10 K. A three-dimensional modified continuum model, coupled with a self-consistent Hartree scheme, was employed to gain insight into the electronic and optical properties of the experimentally studied [Formula: see text]-plane GaN/AlGaN quantum wells. This model confirmed the existence of strong hole localization arising from the combined effects of the built-in polarization field along the growth direction and the alloy fluctuations at the quantum well/barrier interface. However, for electrons these localization effects are less pronounced in comparison to the holes. Furthermore, our calculations show that the attractive Coulomb interaction between electron and hole results in exciton localization. This behavior is in contrast to the picture of independently localized electrons and holes, often used to explain the radiative recombination process in [Formula: see text]-plane InGaN/GaN quantum well systems.

Association of inflammatory cytokines, lipid peroxidation end products and nitric oxide with the clinical severity and fetal outcome in preeclampsia in Indian women.

Preeclampsia is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. The various pathways involved in its etiology include endothelial dysfunction, inflammatory milieu, lipid peroxidation and immunological imbalance. The present study was conducted to evaluate the causative and predictive role of nitric oxide, lipid peroxidation end products (MDA) and inflammatory cytokines (IL-6, TNF-α) in clinical presentation, severity and fetal outcome in preeclampsia. The study population was divided into 3 groups- Non- pregnant females comprising the control population; G1 and G2 groups included normal pregnant and pregnant females with preeclampsia with 50 patients in each group. Nitric Oxide and MDA levels were found to be highest in the preeclamptic patients as compared to other two groups. ROC curve analysis shows the superiority of the inflammatory markers as determinants of severity of preeclampsia which suggests the emerging role of pro inflammatory markers in the various pathological changes in preeclampsia. TNF-α emerged as the best marker in multivariate analysis and thus, has the potential for being used as a marker for PIH. Our study illustrates the multifactorial etiology of preeclampsia involving oxidative stress, proinflammatory milieu and endothelial dysfunction.

Comparisons of apparent mass responses of human subjects seated on rigid and elastic seats under vertical vibration.

The apparent mass (AM) responses of human body seated on elastic seat, without and with a vertical back support, are measured using a seat pressure sensing mat under three levels of vertical vibration (0.25, 0.50 and 0.75 m/s(2) rms acceleration) in 0.50-20 Hz frequency range. The responses were also measured with a rigid seat using the pressure mat and a force plate in order to examine the validity of the pressure mat. The pressure mat resulted in considerably lower AM magnitudes compared to the force plate. A correction function was proposed and applied, which resulted in comparable AM from both measurement systems for the rigid seat. The correction function was subsequently applied to derive AM of subjects seated on elastic seat. The responses revealed lower peak magnitude and corresponding frequency compared to those measured with rigid seat, irrespective of back support and excitation considered.

Comparison of the various lipid ratios and indices for risk assessment in patients of myocardial infarction.

OBJECTIVES: Coronary artery disease (CAD) has emerged as the major cause of morbidity and mortality among Asian Indians in the recent past. The following study was undertaken to assess the predictive value of novel biomarkers of dyslipidemia for risk assessment for CAD in the Indian population. DESIGN AND METHODS: The study group comprised of 100 clinically assessed patients of myocardial infarction and 100 age and sex matched healthy controls. Apolipoprotein-A (Apo-AI) and Apolipoprotein-B (Apo-B) were estimated and small dense LDL was derived mathematically. RESULTS: The cases showed significantly high levels of total serum cholesterol, triglycerides, LDL cholesterol, Apo-B, sdLDL, and non-HDL cholesterol. On carrying out multivariate regression analysis, Lp(a)/HDL ratio emerged as the best determinant of CAD risk CONCLUSION: The above data clearly underlines the role of these novel biomarkers in the risk assessment for CAD in the Indian context.

Epigenetic DNA-(cytosine-5-carbon) modifications: 5-aza-2'-deoxycytidine and DNA-demethylation.

DNA (cytosine-5-carbon) methylation is one of the hallmarks of mammalian chromatin modifications. Distinct methylation pattern can generate synergistic or antagonistic interaction affinities for CpG-islands associated with methylated or unmethylated cytosine binding proteins, which also may dictate histone modifications and dynamic transition between transcriptionally silent or transcriptionally active chromatin states. The enzymes and cofactors associated with DNA-methylation reactions are convincing in terms of chemistry and chemical thermodynamics. The mechanism of demethylation, the candidate enzyme(s) exhibiting direct demethylase activity, and associated cofactors are not firmly established. Use of azanucleosides, such as 5-azacytidine and 5-aza-2'-deoxycytidine (AzadC), in cell culture produces re-expression of certain genes, which otherwise were repressed in association with hypermethylated CpG-rich promoters. Hence the notion developed that AzadC is a demethylating agent. Here we discuss the broad global pictures with the following points: first, chemical definition and recent advances regarding the mechanism of DNA (cytosine-5-carbon) methylation ((Me)CpG-DNA or (Me)CpNpG-DNA formation) and (Me)CpG/(Me)CpNpG-DNA-demethylation, and then with the mechanistic basis of inactivation of DNA-methyltransferase 1 by AzadC. This will clarify that: (i) AzadC has nothing to do with DNA-demethylation; (ii) it cannot prevent even de novo methylation in non-replicating cells; (iii) it can only prevent replication coupled maintenance as well as de novo methylations. Finally, we would like to suggest that terming/designating AzadC as DNA-demethylating agent is a serious misuse of chemistry and chemical terminology.

Molecular targets of (-)-epigallocatechin-3-gallate (EGCG): specificity and interaction with membrane lipid rafts.

Proteomic studies on anticancer activity of Green Tea Catechins (specifically EGCG) are suggesting a large set of protein targets that may directly interact with EGCG and alter the physiology of diseased cells, including cancer. Of notice, benign cells are usually left untouched. Lipid rafts have been recently recognized as signal processing hubs and suggested to be involved in drug uptake by means of endocytosis. These findings are suggesting new insights on the molecular mechanisms of anticancer drugs action. In the membrane, EGCG is hijacked by the laminin receptor (LamR), a lipid raft protein. Similar to aplidin and edelfosin, EGCG alters membrane domains composition also preventing EGF binding to EGFR, imerization of EGFR and relocation of phosphorylated EGFR to lipid rafts. In vitro studies have recently shown that EGCG also binds both DNA and RNA in GpC-rich regions. This event may importantly affect genes function. Moreover, EGCG was shown to inhibit telomerase, topoisomerase II and DNA methyltransferase 1 (DNMT1), thus ultimately affecting chromatin maintenance and remodeling. But another important alternative pathway besides interaction with specific proteins may play an important role in EGCG action: direct targeting of bioactive membrane platforms, lipid rafts. Structural alteration of the platforms deeply impact (and often inactivates) important pathways involving MAP kinases. The key issue is that, important and specific differences in lipid rafts composition have been found in transformed versus benign cells and apoptotic versus non-apoptotic cells. We suggest here that the anticancer activity of Green Tea Catechins against different kind of cancers may find an explanation in direct targeting of lipid rafts by EGCG.

Histone deacetylase and DNA methyltransferase in human prostate cancer.

CpG island hypermethylation and chromatin remodeling play important roles in repression of various genes during malignant transformation. We hypothesized that histone deacetylases (HDACs) and DNA methyltransferases (DNMTase) are associated with prostate cancer and we examined the enzyme activity, gene, and protein expression of HDAC1 and DNMT1 in cell lines and tissues. We found that DNMTase and HDACs activities were two- to threefold higher in cell lines compared to benign prostatic hyperplasia (BPH-1) cell line. Treatment of cells with 5-aza-2'-deoxycytidine decreased the activity of HDAC and DNMTase. The mRNA expression of these genes in BPH-1 cells and BPH tissues was lower than that in prostate cancer cells and tissues. HDAC1 and DNMT1 protein expression was higher in prostate cancer compared to BPH. This is the first report to demonstrate that DNMT1 and HDAC1 levels are up-regulated in prostate cancer compared to BPH, suggesting their roles in inactivation of various genes, by DNA-methylation-induced chromatin-remodeling, in prostate cancer.

Hexachlorocyclohexane-induced behavioural and neurochemical changes in rat.

Effect of chronic oral exposure (10 and 20 mg kg(-1) body wt. for 7, 15 and 30 days) to hexachlorocyclohexane (HCH) on open-field behaviour and activities of cerebral Na+,K+-ATPase, Mg2+-ATPase and acetylcholinesterase (AChE) of rat was evaluated. Motor and grooming activities were altered, whereas vertical exploratory activity was unaffected by HCH. Activities of Na+,K+-ATPase, Mg2+-ATPase and AChE were inhibited significantly by the pesticide. The results suggest that HCH induces impairment of the enzymes involved in synaptic activity, resulting in behavioural alterations.

Detergent solubilisation of phospholipid bilayers in the gel state: the role of polar and hydrophobic forces.

Testing the solubilisation of phosphatidylcholine (PC) bilayers by Triton X-100 reveals that in the gel state, but not in the fluid state, the amount of detergent required to solubilise the phospholipid is highly dependent on the chain length. Saturated C16 and C18 PC are virtually insoluble at 4 degreesC. However, addition of water-soluble reagents that perturb hydrogen bonding, e.g. urea, or of small proportions of non-bilayer lipids, make the bilayers amenable to detergent solubilisation, even at low temperatures. These results are relevant in the explanation of the origin of detergent-resistant membrane fragments as found, e.g. in caveolae or 'rafts'.

Red edge excitation shift emission spectroscopic investigation of serum albumins and serum albumin-bilirubin complexes.

The microenvironments around the intrinsic and extrinsic fluorophores in bovine and human serum albumins as well as their complexes with bilirubin have been visualized by red edge excitation shift (REES) emission spectroscopic investigation. The two albumins and their bilirubin complexes in aqueous buffered solutions (pH 7.5) do not exhibit any appreciable shift in their emission maxima, upon gradual change in excitation wavelength towards the red edge of their respective absorption band. The addition of Triton X-100 triggers REES emission in both the fluorophores. The observations suggest that the microenvironment around the flurophores are not so rigid, and even the extrinsic flurophore bilirubin having two carboxylic acid groups acts as a hydrophobic non-polar molecule when bound to albumins. The ligand binding domains (receptor sites) are large enough and incorporation of Triton X-100 makes the fluorophore environments rigid and subtle polarity may also be induced. Whereas small polar molecules like CHCl3, ANS and L-trp fail to induce REES emission in either of the fluorophores.

Spectroscopic probes of the individual and combined effects of Triton X-100 and chloroform on serum albumins and serum-albumin.bilirubin complexes.

The effects of the non-ionic surfactant Triton X-100 on the biphasic induced CD spectra of bilirubin complexes of human and bovine serum albumins (HSA and BSA) are divergent. While Triton X-100 inverts the induced CD spectrum of HSA.bilirubin, this surfactant enhances the ellipticity values of induced CD of BSA.bilirubin without inversion. The effect of Triton X-100 on the characteristic ultraviolet-CD spectra of the albumins are similar; both the albumins are denatured from their native globular structures. The anionic surfactant SDS, unlike non-ionic Triton X-100, dislodges the ligand from its protein complexes, indicating that both electrostatic and hydrophobic forces are involved in binding of bilirubin to the albumins. The aprotic solvent chloroform inverts the biphasic induced CD spectra of HSA.bilirubin and BSA.bilirubin, whereas CHCl3 has relatively little effect on the ultraviolet CD spectra of the albumins. The combined effect of Triton X-100 and CHCl3 shows that the effect of CHCl3 predominates over that of Triton X-100. The perturbing effects of Triton X-100 and CHCl3 on the CD or induced CD spectra of the proteins or their bilirubin complexes are reversible, and independent of the order in which components were added. The observations suggest that the denaturation of the albumins by Triton X-100 or solvation of CHCl3 within albumins markedly alter the internal topography or dynamics of the receptor sites, triggering alterations of the chirality of the bound pigment in sign and/or magnitude.

Spatial memory deficits following stimulation of hippocampal 5-HT1B receptors in the rat.

In this study we examined a possible contribution of serotonin (5-hydroxytryptamine, 5-HT) to spatial memory performance in the rat. Rats were trained to run in a radial maze in a manner that involved two kinds of memory function, i.e. working memory and reference memory. They received intrahippocampal microinjections of a 5-HT1A [8-hydroxy-2-(di-n-propylamino)tetralin or 8-OH-DPAT], or a 5-HT1B [3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one or CP-93,129] receptor agonist, and a muscarinic receptor antagonist (scopolamine). 8-OH-DPAT (5 micrograms/microliters), like injections of saline, induced no change in performance levels. In contrast, rats suffered an impairment in both reference and working memory following injection of scopolamine (10 micrograms/microliters). CP-93,129 induced a higher frequency of reference memory errors than of working memory errors at the intermediate (10 micrograms/microliters) and higher doses (16 micrograms/microliters). Thus, the stimulation of 5-HT1B receptors in the CA1 field of the dorsal hippocampus impairs the performance of rats in a spatial learning task.

Fluorimetric probes of the individual and competitive binding of 1-anilinonaphthalene-8-sulfonate, eosine and fluorescene to bovine serum albumin.

Fluorescence of 1-anilinonaphthalene-8-sulfonate (ANS) is greatly enhanced on its binding to bovine serum albumin (BSA). Fluorimetric titration shows that three ANS molecules bind per BSA molecule. The enhanced fluorescence of BSA-ANS is quenched by eosine (EOS); and one EOS physically displaces one ANS bound to BSA. The enhanced fluorescence of free ANS in the hydrophobic environment of the nonionic surfactant Triton X 100 is also quenched by EOS but by an energy transfer mechanism. The dye fluorescene (FLSN) also quenches the fluorescence of BSA-bound ANS, but by the energy transfer mechanism. The binding region of ANS in BSA has been speculated.

Protein kinase C dependent and independent activation of phospholipase A2 under calcium ionophore (A23187) exposure in rabbit pulmonary arterial smooth muscle cells.

Exposure of rabbit pulmonary arterial smooth muscle cells to the calcium ionophore A23187, dose-dependently stimulates arachidonic acid (AA) release and phospholipase A2 (PLA2) activity. The protein kinase C (PKC) inhibitor, sphingosine does not prevents AA release and PLA2 activity caused by low doses of A23187. In contrast, sphingosine markedly prevents AA release and PLA2 activity caused by higher doses of A23187. PKC activity profile indicates that treatment of the cells with low doses of A23187 does not cause significant alteration of PKC translocation from cytosol to membrane whereas higher concentrations of the ionophore dose-dependently enhance PKC translocation from cytosol to membrane in the smooth muscle cells.

Evaluation of different surgical procedures in filarial lymphoedema of lower extremity.

Ninety-six cases of different stages of lymphoedema of inferior extremity were taken for study. Twenty-four patients with early lymphoedema (stage II) were subjected to lymphonodovenous shunt (LNVS) operation; 54 patients of late lymphoedema with skin changes (Stage IV) were subjected to Charles' operation and 18 patients with late lymphoedema without skin changes (stage III) were subjected either to Sistrunk's or Thompson's operation. All the results were studied, evaluated and compared. The cases subjected to LNVS operation had a rapid relief of lymphoedema in the early postoperative period followed by slow reduction. Patients subjected to Charles' operation had immediate volume and circumference reduction and take up of skin grafting was 84%. The cases subjected to Thompson's operation did not have satisfactory reduction in volume and circumference postoperatively. There were a few minor postoperative complications in all these procedure, infection being most notable in those who had undergone Charles' operation. It is concluded that while excisional surgery, such as Charles' operation becomes necessary for late stages of lymphoedema, which have progressed to elephantiasis, nodovenous shunt alone is sufficient to relieve early stages of lymphoedema due to filariasis.