The neglected role of relative humidity in the interannual variability of urban malaria in Indian cities.

The rapid pace of urbanization makes it imperative that we better understand the influence of climate forcing on urban malaria transmission. Despite extensive study of temperature effects in vector-borne infections in general, consideration of relative humidity remains limited. With process-based dynamical models informed by almost two decades of monthly surveillance data, we address the role of relative humidity in the interannual variability of epidemic malaria in two semi-arid cities of India. We show a strong and significant effect of humidity during the pre-transmission season on malaria burden in coastal Surat and more arid inland Ahmedabad. Simulations of the climate-driven transmission model with the MLE (Maximum Likelihood Estimates) of the parameters retrospectively capture the observed variability of disease incidence, and also prospectively predict that of 'out-of-fit' cases in more recent years, with high accuracy. Our findings indicate that relative humidity is a critical factor in the spread of urban malaria and potentially other vector-borne epidemics, and that climate change and lack of hydrological planning in cities might jeopardize malaria elimination efforts.

Treatment Effects and Lip Profile Changes Following Surgical Mandibular Advancement Versus Premolar Extractions in Class II Div 1 Malocclusion: A Randomized Controlled Trial.

ABSTRACT: No randomized controlled trial has compared the treatment outcome between surgical mandibular advancement and premolar extractions in class II malocclusion. This 2-arm parallel randomized controlled trial evaluated the treatment effects and lip profile changes in skeletal class II adult patients subjected to bilateral sagittal split ramus osteotomy for mandibular advancement and those treated with premolar extractions. Seventy skeletal class II patients were accessed and forty-six subjects who fulfilled inclusion criteria were distributed randomly into Group CG (patients: 23, mean age: 21.28 ±â€Š2.69 years) and Group SG (patients: 23, mean age: 21.15 ±â€Š2.64 years). Group CG was subjected to extraction of maxillary first premolars and mandibular second premolars followed by implant supported space closure and Group SG was managed by surgical mandibular advancement. Skeletal, dental, and soft-tissue changes were analyzed. The study was single-blinded (statistical analyzer). Groups were closely matched for baseline parameters. In the present trial there was no loss to follow-up. Though overjet and overbite were optimized in both the groups but significant improvement was seen in surgical cases. Group CG demonstrated statistically significant point "A" remodeling, dentoalveolar changes, and increase in nasolabial angle. Group SG exhibited significant sagittal and vertical skeletal improvement and lip position change. Surgical mandibular advancement was found to be a better treatment modality compared to premolars extraction for managing skeletal class II div 1 malocclusion as it permits greater improvement of the profile and skeletal relationship.

Temporally Distinct Roles for the Zinc Finger Transcription Factor Sp8 in the Generation and Migration of Dorsal Lateral Ganglionic Eminence (dLGE)-Derived Neuronal Subtypes in the Mouse.

Progenitors in the dorsal lateral ganglionic eminence (dLGE) are known to give rise to olfactory bulb (OB) interneurons and intercalated cells (ITCs) of the amygdala. The dLGE enriched transcription factor Sp8 is required for the normal generation of ITCs as well as OB interneurons, particularly the calretinin (CR)-expressing subtype. In this study, we used a genetic gain-of-function approach in mice to examine the roles Sp8 plays in controlling the development of dLGE-derived neuronal subtypes. Misexpression of Sp8 throughout the ventral telencephalic subventricular zone (SVZ) from early embryonic stages, led to an increased generation of ITCs which was dependent on Tshz1 gene dosage. Additionally, Sp8 misexpression impaired rostral migration of OB interneurons with clusters of CR interneurons seen in the SVZ along with decreased differentiation of calbindin OB interneurons. Sp8 misexpression throughout the ventral telencephalon also reduced ventral LGE neuronal subtypes including striatal projection neurons. Delaying Sp8 misexpression until E14-15 rescued the striatal and amygdala phenotypes but only partially rescued OB interneuron reductions, consistent with an early window of striatal and amygdala neurogenesis and ongoing OB interneuron generation at this late stage. Our results demonstrate critical roles for the timing and neuronal cell-type specificity of Sp8 expression in mouse LGE neurogenesis.

Foxo1 is a downstream effector of Isl1 in direct pathway striatal projection neuron development within the embryonic mouse telencephalon.

Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15.5 with a modest recovery by E18.5. Although Foxo1 is enriched in the direct pathway SPNs at embryonic stages, it is expressed in both direct and indirect pathway SPNs at postnatal time points as evidenced by co-localization with EGFP in both Drd1-EGFP and Drd2-EGFP BAC transgenic mice. Foxo1 was not detected in striatal interneurons as marked by the transcription factor Nkx2.1. Conditional knockout of Foxo1 using Dlx5/6-CIE mice results in reduced expression of the SPN marker Darpp-32, as well as in the direct pathway SPN markers Ebf1 and Zfp521 within the embryonic striatum at E15.5. However, this phenotype improves in the conditional mutants by E18.5. Interestingly, the Foxo family members, Foxo3 and Foxo6, remain expressed at late embryonic stages in the Foxo1 cKOs unlike the Isl1 cKOs where Foxo1/3/6 as well as the Foxo1/3 target Bach2 are all reduced. Taken together, these findings suggest that Foxo-regulated pathways are downstream of Isl1 in the survival and/or differentiation of direct pathway SPNs.

Effect of surgical mandibular advancement on pharyngeal airway dimensions: a three-dimensional computed tomography study.

The aim of this study was to quantify the changes in pharyngeal airway space (PAS) in patients with a skeletal class II malocclusion managed by bilateral sagittal split ramus osteotomy for mandibular advancement, using three-dimensional (3D) registration. The sample comprised 16 patients (mean age 21.69±2.80 years). Preoperative (T0) and postoperative (T1) computed tomography scans were recorded. Linear, cross-sectional area (CSA), and volumetric parameters of the velopharynx, oropharynx, and hypopharynx were evaluated. Parameters were compared with paired samples t-tests. Highly significant changes in dimension were measured in both sagittal and transverse planes (P<0.001). CSA measurements increased significantly between T0 and T1 (P<0.001). A significant increase in PAS volume was found at T1 compared with T0 (P<0.001). The changes in PAS were quantified using 3D reconstruction. Along the sagittal and transverse planes, the greatest increase was seen in the oropharynx (12.16% and 11.50%, respectively), followed by hypopharynx (11.00% and 9.07%) and velopharynx (8.97% and 6.73%). CSA increased by 41.69%, 34.56%, and 28.81% in the oropharynx, hypopharynx, and velopharynx, respectively. The volumetric increase was greatest in the oropharynx (49.79%) and least in the velopharynx (38.92%). These established quantifications may act as a useful guide for clinicians in the field of dental sleep medicine.

Prevalence of psychiatric morbidity among urban elderlies: Lucknow elderly study.

BACKGROUND: Paucity of systematic studies in elderly mental health in an aging population is an urgent need, which is required to address services and planning issues for health. AIM: The present study aims to investigate the distribution of physical, neuropsychiatric, and cognitive disorders of a community sample of elderlies with certain socioeconomic data. MATERIALS AND METHODS: A door-to-door household survey was conducted to identify houses with elderlies (≥55 years) in two urban localities of Lucknow. Mini mental state examination (MMSE), Survey Psychiatric Assessment Schedule (SPAS)/Mood Disorder Questionnaire (MDQ) and physical and neurological examination were used for screening all consenting elderlies. MMSE positive participants were assessed on Cambridge Mental Disorders of the Elderly Examination-Revised for diagnosis of cognitive disorders; SPAS/MDQ positives were assessed on Schedule for Clinical Assessment in Neuropsychiatry based clinical interview for diagnosis of neuropsychiatric disorders other than cognitive disorders (using ICD-10 criteria). Routine and indicated laboratory/radiological investigations on all and on MMSE/SPAS (organic section) positive/physically ill participants respectively were done to confirm organic and/or physical illness. Only percentages were calculated to find the distribution of morbidity. RESULTS: The sample had proportionate age structure as that of the surveyed population and had balanced gender representation in each age deciles. Prevalence of neuropsychiatric disorders (with/without comorbidities) was 11.8% in the elderlies (60 years and above) highest being in the 60-69 years age group. Being women and of lower socioeconomic status was more commonly associated with a neuropsychiatric diagnosis. 7.6% of the elderlies had cognitive impairment. Overall findings suggest a prevalence rate of 17.34% of total psychiatric morbidity among elderlies. A significant number had comorbid physical illness diagnoses. CONCLUSION: More than half the elderlies had some diagnosable physical or mental ailment. The study familiarizes us to the significant amount of physical and psychiatric comorbidity in the particular age group. About one-fifth was found to suffer from psychiatric morbidity, which any health services for the elderly should be oriented towards.

Successful management of primary nontuberculous mycobacterial infection of hepatic allograft following orthotopic liver transplantation for hepatitis C.

Nontuberculous mycobacteria are a rare cause of disease in solid organ and hematopoietic stem cell transplant recipients. The impact of mycobacterial infections in transplant recipients necessitates prompt diagnosis and early initiation of therapy. However, diagnosis remains difficult and there is a lack of specific recommendations for the choice of anti-mycobacterial drugs, duration of therapy, and monitoring of graft function as well as immunosuppression in these patients. Issues involved in the management are illustrated by an index case of hepatic allograft infection due to Mycobacterium avium complex.

Image contrast in X-ray reflection interface microscopy: comparison of data with model calculations and simulations.

The contrast mechanism for imaging molecular-scale features on solid surfaces is described for X-ray reflection interface microscopy (XRIM) through comparison of experimental images with model calculations and simulated measurements. Images of elementary steps show that image contrast is controlled by changes in the incident angle of the X-ray beam with respect to the sample surface. Systematic changes in the magnitude and sign of image contrast are asymmetric for angular deviations of the sample from the specular reflection condition. No changes in image contrast are observed when defocusing the condenser or objective lenses. These data are explained with model structure-factor calculations that reproduce all of the qualitative features observed in the experimental data. These results provide new insights into the image contrast mechanism, including contrast reversal as a function of incident angle, the sensitivity of image contrast to step direction (i.e. up versus down), and the ability to maximize image contrast at almost any scattering condition defined by the vertical momentum transfer, Q(z). The full surface topography can then, in principle, be recovered by a series of images as a function of incident angle at fixed momentum transfer. Inclusion of relevant experimental details shows that the image contrast magnitude is controlled by the intersection of the reciprocal-space resolution function (i.e. controlled by numerical aperture of the condenser and objective lenses) and the spatially resolved interfacial structure factor of the object being imaged. Together these factors reduce the nominal contrast for a step near the specular reflection condition to a value similar to that observed experimentally. This formalism demonstrates that the XRIM images derive from limited aperture contrast, and explains how non-zero image contrast can be obtained when imaging a pure phase object corresponding to the interfacial topography.

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

The burden of malaria in Ahmedabad city, India: a retrospective analysis of reported cases and deaths.

Owing to the paucity of accurate information on the burden of malaria in urban India, a retrospective, epidemiological study was carried out in Ahmedabad city, which has a population of about 3 million. Surveillance data for the years 1965-1998 showed a gradual resurgence of malaria between 1967 to 1976, followed by waves of low and high incidences. Plasmodium vivax always predominated but the proportion of cases attributed to P. falciparum increased markedly from 1983. When the surveillance data and health records of the major public and private health facilities in the city were analysed, for the period between 1991 and 1998, P. vivax was found to account for 69% of all malaria cases and P. falciparum for the other 31%. The incidence of infection with each Plasmodium species showed seasonal variation, with that of P. vivax increasing from January to September but then declining as the incidence of P. falciparum increased. The age-specific differences seen in incidence were not statistically significant (P=0.7). The annual numbers of malaria-attributable deaths were strongly correlated with the incidence of P. falciparum (r=0.88). The malaria incidence detected (37431 cases, representing a mean annual incidence of 12.2 cases/1000) was nine times greater than that officially reported (4119 cases, or 1.3 cases/1000 each year). Similarly, the annual malaria-attributable mortality detected (22 deaths/million) was far higher than that officially notified (0.3 death/million). The results of the retrospective analysis not only provide a more accurate, baseline estimate of the burden of malaria in an urban area of India but also clearly indicate the need for a much more efficient health-information system, for recording and managing malaria in such a setting.

Discrete subvalvular aortic stenosis in adults.

Discrete subvalvular aortic stenosis is a relatively rare condition in adults. It is often diagnosed during first decade of life especially in association with other congenital malformations. Isolated form of discrete subvalvular aortic stenosis may however silently progress from innocent murmurs of childhood and adolescence to symptomatic left ventricular outflow tract obstruction in adults. Certain overt and subtle morphological abnormalities may underlie the initial expression as well as high recurrence rates after surgical resection of sub aortic membrane. Though surgical resection is the only treatment available, debate on the surgical technique and appropriate timing of surgery continues. Close followup with serial echocardiographic examinations in patients detected to have functional murmurs during childhood may be helpful in early detection of subvalvular aortic stertosis.

Calmodulin binding to the C-terminus of the small-conductance Ca2+-activated K+ channel hSK1 is affected by alternative splicing.

We identified three splice variants of hSK1 whose C-terminal structures are determined by the independent deletion of two contiguous nucleotide sequences. The upstream sequence extends 25 bases in length, is initiated by a donor splice site within exon 8, and terminates at the end of the exon. The downstream sequence consists of nine bases that compose exon 9. When the upstream sequence (hSK1(-)(25b)) or both sequences (hSK1(-)(34b)) are deleted, truncated proteins are encoded in which the terminal 118 amino acids are absent. The binding of calmodulin to these variants is diminished, particularly in the absence of Ca2+ ions. The first 20 amino acids of the segment deleted from hSK1(-)(25b) and hSK1(-)(34b) contain a 1-8-14 Ca2+ calmodulin binding motif, and synthetic oligopeptides based on this region bind calmodulin better in the presence than absence of Ca2+ ions. When the downstream sequence (hSK1(-)(9b)) alone is deleted, only the three amino acids A452, Q453, and K454 are removed, and calmodulin binding is not reduced. On the basis of the relative abundance of mRNA encoding each of the four isoforms, the full-length variant appears to account for most hSK1 in the human hippocampus, while hSK1(-)(34b) predominates in reticulocytes, and hSK1(-)(9b) is especially abundant in human erythroleukemia cells in culture. We conclude that the binding of calmodulin by hSK1 can be modulated through alternative splicing.

Dynamics of malaria transmission under changing ecological scenario in and around Nanak Matta Dam, Uttaranchal, India.

To understand the transmission dynamics of malaria in three different ecotypes, namely watershed (forest), seepage (Nanak Matta Dam) and plain (non-forest, non-dam) areas of Nainital and Udham Singh Nagar districts of Uttaranchal, entomological and parasitological investigations were carried out from July 1996 to June 1997. In the three ecotypes, average per man hour densities of adult vector species in human dwellings and cattlesheds recorded were high for Anopheles culicifacies from April to September and October to March for An. fluviatilis. Prevalence of both An. culicifacies and An. fluviatilis was higher in the forest area as compared to other two areas. Observations on gonotrophic condition revealed endophilic tendency of both vector species. Higher number of both vector species were found in outdoor than indoor during night human bait collections. Out of 864 specimens of An. fluviatilis dissected, one showed natural infection of sporozoites in salivary glands in the month of November from the forest area only. Sibling species study of An. fluviatilis revealed the presence of species S for the first time in the forest area. Parasitological investigations also depicted high incidence of malaria in the forest area as compared to other two areas. Overall results from the study indicated active malaria transmission in the forest area.

Comparison of ministernotomy with minithoracotomy regarding postoperative pain and internal mammary artery characteristics.

PURPOSE: This prospective clinical study focuses on postoperative pain and internal mammary artery (IMA) characteristics after ministernotomy versus left anterior minithoracotomy. METHOD: Patients were studied in two groups. Group A consisted of 267 consecutive single vessel (IMA to left anterior descending artery (LAD)) minimally invasive direct coronary artery bypass (MIDCAB) patients using ministernotomy from the tip of the xiphoid to the fourth intercostal space. Group B consisted of the same number of MIDCAB patients operated on through anterolateral minithoracotomy. Pain was graduated using the visual analog scale (VAS). Internal mammary artery (IMA) characteristics were compared in both the groups. RESULTS: Postoperative pain was not significant statistically on postop day (POD) 1 in either of the groups (p = 0.07). From POD 2 onwards Group A patients had less pain than Group B patients (p < 0.05), and the pain medication requirement from POD 2 onwards was less in Group A than in Group B. Length of harvested IMA was 15.6 +/- 2.1 cm in Group A as compared to 10.4 +/- 2.2 cm in Group B (p < 0.05). Free flow of IMA in group A was 56 +/- 16 ml/min., whereas in Group B the flow was 50 +/- 14 ml/min. (p = 0.04). CONCLUSION: Compared to patients undergoing MIDCAB using ministernotomy, anterolateral minithoracotomy patients suffer more pain from POD 2 onwards and their postoperative pain medication requirement is also higher. Length and free flow of IMA is better in patients operated on for MIDCAB using ministernotomy. Thus, ministernotomy is a better approach than minithoracotomy in terms of postoperative pain and IMA characteristics for single-vessel MIDCAB patients.

Discrete subvalvular aortic stenosis.

Discrete Subaortic Stenosis is one of the many lesions responsible for left ventricular outflow tract (LVOT) obstruction. It may present as in an isolated from as membranous or fibromuscular ring below the aortic valve or in association with other congenital anamolies such as VSD, PDA, coarctation of aorta, hypoplastic aortic annulus, double chamber right ventricle among others. The condition is rarely diagnosed antenataly or in infancy but often manifests in the first decade of life with features of progressive LVOT obstruction, LV hypertrophy and dysfunction aortic regurgitation due to damage to the aortic cusps because of the jet from the subaortic narrowing which may also render the aortic valve prone to infective endocarditis. Interaction of genetic predisposition and morphologically deformed long and narrow LVOT cause rheological abnormalities and increased shear stress in the region of subaortic stenosis and seem to be the main etiological factor alongwith poorly defined role of more extensive but subtle changes in the LV endocardium. Condition can be easily diagnosed by cross-sectional and Doppler echocardiography and confirmed by demonstrating a pressure gradient below aortic valve on cardiac catheterisation and LV angiography. Surgical membranectomy alongwith myotomy or myomectomy remain the mainstay of treatment but long term results are not satisfactory as there is a high rate of recurrences requiring reoperations. A close follow up with serial echocardiographic examinations is very helpful in early detection of subaortic obstruction in patients who have so called functional murmurs in the childhood.

Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver.

BACKGROUND: Cold preservation of the liver followed by reperfusion results in sinusoidal endothelial cell (SEC) apoptosis. Calpain-like activity is dramatically increased during reperfusion and inhibition of calpains results in lower graft injury and longer survival. Recently, calpains have been implicated in inducing apoptosis. Our aim was to determine the effect of calpain inhibition on SEC apoptosis. METHODS: Livers were stored in the University of Wisconsin solution for 24 hr (survival conditions) and 40 hr (nonsurvival conditions) and ex vivo reperfused for 1 hr at 37 degrees C. Calpain-like activity was inhibited in some experiments using an i.p. injection of a selective inhibitor 2 hr before explantation. Apoptosis was quantified using the terminal deoxynucleotidyl trans. ferase-mediated dUTP nick end-labeling assay. Cross-inhibition by the inhibitor was determined for caspases 1 and 3. RESULTS: Apoptosis of exclusively the SEC was a key feature of reperfusion injury after both storage periods in University of Wisconsin solution after 1 hr normothermic reperfusion. Inhibition of calpain activity with Cbz-Val-Phe methyl ester resulted in a 50% reduction of apoptotic SEC in the 40-hr preserved liver, and an almost complete abrogation of SEC apoptosis after 24 hr preservation. Only minimal cross-inhibition of caspases was determined at high concentrations in vitro by the calpain inhibitor. CONCLUSION: Apoptosis of exclusively SEC is a key feature of reperfusion injury partially mediated through calpain-dependent processes. Calpain inhibition reduces the number of apoptotic SEC. Based on these data and our previous work, calpain inhibition may prove to be useful in clinical transplantation.

Paired ventricular pacing: an alternative therapy for postoperative junctional ectopic tachycardia in congenital heart disease.

Junctional ectopic tachycardia (JET) is one of the most life-threatening postoperative arrhythmias in children with congenital heart disease, and medical management is difficult. Paired ventricular pacing (PVP) may provide a safe alternative mode of management. We evaluated the safety and efficacy of PVP for the management of postoperative JET in patients with congenital heart disease. A retrospective collection of data was done from 1981-1995. PVP was successfully tried in five postoperative patients (age range: 37 days to 22 years, median: 10 months). Onset of JET was 3-60 hours (mean +/- SD, 19 +/- 23 hours) postoperatively. The maximal JET rate was 261 +/- 39 beats/min. PVP was used as the first line of management in three patients and was successful in all patients. It resulted in an instantaneous increase in blood pressure from 66 +/- 9 to 94 +/- 15 mmHg (42% increase) and was required for 12 +/- 14 hours (range 2-36 hours). No complications were noted. Therefore, in our experience, this is a safe alternative modality for the control of postoperative JET.