Caries Incidence Is Associated with Wasting among Cambodian Children.

Evidence suggests that dental caries is associated with chronic and acute malnutrition, manifested as stunting and wasting in children. However, studies have not always appropriately accounted for confounding factors or for the temporal ordering between exposure and outcome. This study examined relationships between the development of caries lesions with subsequent stunting and wasting outcomes using data from a population-based cohort in Cambodia. Caries incidence was assessed based on the presence of a new cavitated carious lesion or a new pulpally involved lesion across a 6-mo observation period. Anthropometric measurements were taken at regular intervals. Effects of carious lesions on stunting and wasting were assessed using inverse probability treatment weighting, adjusting for potential confounders, using z scores for height-for-age (HAZ) and weight-for-height (WHZ) as outcomes. In total, 894 children (mean age 20 mo at baseline) were followed over 2 y. At baseline, 350 (39.1%) were identified as having stunting malnutrition. At follow-up, 58 (6.5%) had a new pulpally involved lesion. There was no association between incidence of cavitated or pulpally involved carious lesions at follow-up and stunting (relative risk [RR] = 1.06; 95% confidence interval [CI]: 0.75, 1.50). The incidence of pulpally involved carious lesions had an effect on wasting prevalence (WHZ <-2; RR = 1.35; 95% CI: 0.70, 2.62) and WHZ scores (average treatment effect = -0.294; 95% CI: -0.538, -0.050). This study offers evidence that the development of pulpally involved carious lesions has an effect on WHZ scores. Oral health promotion and clinical prevention and management of dental caries should be explored as interventions to promote normal growth and development among preschool children, particularly in low-income settings.

Improved multidetector asymmetrical-flow field-flow fractionation method for particle sizing and concentration measurements of lipid-based nanocarriers for RNA delivery.

Lipid-based nanoparticles for RNA delivery (LNP-RNA) are revolutionizing the nanomedicine field, with one approved gene therapy formulation and two approved vaccines against COVID-19, as well as multiple ongoing clinical trials. As for other innovative nanopharmaceuticals (NPhs), the advancement of robust methods to assess their quality and safety profiles-in line with regulatory needs-is critical for facilitating their development and clinical translation. Asymmetric-flow field-flow fractionation coupled to multiple online optical detectors (MD-AF4) is considered a very versatile and robust approach for the physical characterisation of nanocarriers, and has been used successfully for measuring particle size, polydispersity and physical stability of lipid-based systems, including liposomes and solid lipid nanoparticles. However, the unique core structure of LNP-RNA, composed of ionizable lipids electrostatically complexed with RNA, and the relatively labile lipid-monolayer coating, is more prone to destabilization during focusing in MD-AF4 than previously characterised nanoparticles, resulting in particle aggregation and sample loss. Hence characterisation of LNP-RNA by MD-AF4 needs significant adaptation of the methods developed for liposomes. To improve the performance of MD-AF4 applied to LNP-RNA in a systematic and comprehensive manner, we have explored the use of the frit-inlet channel where, differently from the standard AF4 channel, the particles are relaxed hydrodynamically as they are injected. The absence of a focusing step minimizes contact between the particle and the membrane, reducing artefacts (e.g. sample loss, particle aggregation). Separation in a frit-inlet channel enables satisfactory reproducibility and acceptable sample recovery in the commercially available MD-AF4 instruments. In addition to slice-by-slice measurements of particle size, MD-AF4 also allows to determine particle concentration and the particle size distribution, demonstrating enhanced versatility beyond standard sizing measurements.

COP1 Controls Abiotic Stress Responses by Modulating AtSIZ1 Function through Its E3 Ubiquitin Ligase Activity.

Ubiquitination and sumoylation are essential post-translational modifications that regulate growth and development processes in plants, including control of hormone signaling mechanisms and responses to stress. This study showed that COP1 (Constitutive photomorphogenic 1) regulated the activity of Arabidopsis E3 SUMO (Small ubiquitin-related modifier) ligase AtSIZ1 through its E3 ubiquitin ligase activity. Yeast two hybrid analysis demonstrated that COP1 and AtSIZ1 directly interacted with one another, and subcellular localization assays indicated that COP1 and AtSIZ1 co-localized in nuclear bodies. Analysis of ubiquitination showed that AtSIZ1 was polyubiquitinated by COP1. The AtSIZ1 level was higher in cop1-4 mutants than in wild-type seedlings under light or dark conditions, and overexpression of a dominant-negative (DN)-COP1 mutant led to a substantial increase in AtSIZ1 accumulation. In addition, under drought, cold, and high salt conditions, SUMO-conjugate levels were elevated in DN-COP1-overexpressing plants and cop1-4 mutant plants compared to wild-type plants. Taken together, our results indicate that COP1 controls responses to abiotic stress by modulation of AtSIZ1 levels and activity.

Arabidopsis HIGH PLOIDY2 Sumoylates and Stabilizes Flowering Locus C through Its E3 Ligase Activity.

Flowering Locus C (FLC), a floral repressor, plays an important role in flowering. The mechanisms regulating FLC gene expression and protein function have been studied extensively; however, post-translational regulation of FLC remains unclear. Here, we identified Arabidopsis HIGH PLOIDY2 (HPY2) as an E3 SUMO ligase for FLC. In vitro and vivo pull-down assays showed that FLC physically interacts with HPY2. In vitro assays showed that the stimulation of FLC sumoylation by HPY2 was dependent on SUMO-activating enzyme E1 and -conjugating enzyme E2, indicating that HPY2 was an E3 SUMO ligase for FLC. In transgenic plants, inducible HPY2 overexpression increased the concentration of FLC, indicating that HPY2 stabilized FLC through direct sumoylation. Flowering time in hpy2-2 mutants was shorter than in wild-type plants under long- and short-day conditions, with a greater effect under short-day conditions, and FLC was downregulated in hpy2-2 mutants. These data indicate that HPY2 regulates FLC function and stability at both the transcriptional and post-translational levels through its E3 SUMO ligase activity.

Improving the provision of the Basic Package of Oral Care (BPOC) in Cambodia.

UNLABELLED: Since 1992, 330 medical nurses have been trained to provide basic oral health care (including ART restorations and dental extractions) in remote areas of Cambodia. However, a range of barriers prevent dental nurses from providing these services, especially a lack of dental materials and instruments. OBJECTIVES: To increase dental nurse (DN) outputs through the regular provision of dental materials and instruments. To improve cross-infection control procedures through the provision of necessary equipment, supplies and training. METHODS: Six health centres with active DNs participated; three (experimental) health centres received sufficient supplies of dental instruments and materials for one year, and 3-monthly visits by a dentist from the Ministry of Health. The other three health centres (control) did not. RESULTS: During the project period, the experimental group extractions increased to an average of 119 extractions per quarter (a three-fold increase compared to the baseline), 51 ART restorations, and improved compliance with cross-infection infection control protocols. In the control group the number of extractions remained similar to baseline and no ART restorations were placed. CONCLUSIONS: The provision of the BPOC increased in the health centres when sufficient supplies of dental materials and instruments were provided. Increased monitoring and communication with MOH dental colleagues was also associated with the increased outputs and resulted in improved compliance with cross-infection control protocols. The MOH should increase supplies to DNs and provide ongoing monitoring and support in order to improve the access to and quality of dental care provided in rural Cambodia.

Sildenafil (Viagra) augments sodium nitroprusside-induced but not nitroglycerin-induced hypotension in dogs.

UNLABELLED: We investigated whether sildenafil citrate (Viagra) may reduce the dose of nitrovasodilators to induce deliberate hypotension. Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. Sodium nitroprusside (SNP; 1-16 microg. kg(-1). min(-1)) or nitroglycerin (NTG; 2-32 microg. kg(-1). min(-1)) was IV given to induce hypotension. The study consisted of two occasions, in a random order, in each animal: one with sildenafil pretreatment (1 mg/kg IV followed by 0.3 mg. kg(-1). h(-1)) and the other without to serve as a control. Hemodynamic variables were continuously monitored. Plasma cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay. Both SNP and NTG produced dose-dependent decreases in mean arterial blood pressure without affecting the heart rate in the presence as well as in the absence of sildenafil. Systemic vascular resistance index and mean pulmonary arterial pressure were also decreased. The magnitude of mean arterial blood pressure and systemic vascular resistance index reductions caused by SNP was augmented by sildenafil, whereas that caused by NTG was not affected. Neither SNP nor NTG alone altered the plasma cGMP concentrations. Sildenafil increased the plasma cGMP concentration, which was further increased by SNP but not affected by NTG. These results indicate that sildenafil may reduce the dose of SNP in producing deliberate hypotension in the dog. The potentiation of SNP-induced hypotension by sildenafil may be related to an augmented accumulation of cGMP. IMPLICATIONS: Sildenafil may reduce the dose of sodium nitroprusside required to induce deliberate hypotension and hence the potential for cyanide toxicity.

Choroidal perfusion perturbations in non-neovascular age related macular degeneration.

AIM: Choroidal perfusion, affected in age related macular degeneration (AMD), is difficult to objectively assess given the overlying retinal circulation. This study more objectively compared choroidal perfusion parameters in a group with non-neovascular AMD to an unaffected age matched control group. METHODS: 21 non-neovascular AMD subjects and 21 age matched control subjects without evidence of AMD underwent assessment of their choroidal blood flow in a case-control study. Scanning laser ophthalmoscope indocyanine green (ICG) angiograms were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary retina were evaluated by producing a graph of intensity of fluorescence of each area over time. The mean of the filling times and the heterogeneity of the filling times were assessed. RESULTS: The means of the filling times within the perifoveal regions and the hetereogeneity of the filling times between regions within the same eyes were significantly greater in the AMD patients compared with the control subjects. CONCLUSIONS: Delayed and heterogeneous filling of the choroid was objectively demonstrated in eyes with non-neovascular AMD compared with age matched controls without evidence of AMD, using an area dilution analysis technique applied to ICG angiography.

Effects of vortex pinning and thermal fluctuations on the Josephson plasma resonance in Tl2Ba2CaCu2O8 and YBa2Cu3O6.5.

We investigated the temperature dependence and c-axis magnetic field dependence of the Josephson plasma resonance in optimally doped Tl2Ba2CaCu2O8 thin films and underdoped YBa2Cu3O6.5 (YBCO) ortho-II single crystals using infrared spectroscopy. We obtained the c-axis penetration depths, at low temperature, in zero fields of about 20 and 7 microm, respectively. While the temperature dependencies of the resonances in the two compounds are very similar, the magnetic field dependence in YBCO is much weaker. We attribute this weak magnetic field dependence to the lower anisotropy of YBCO and interpret the observed behaviors in terms of thermal fluctuations and pinning of pancake vortices.

Is Schistosoma mansoni replacing Schistosoma haematobium in the Fayoum?

Schistosoma mansoni is progressively replacing S. haematobium along the Nile River in Egypt. This change has occurred in the past 15-20 years following construction of the Aswan High Dam in the 1960s. The cause is a shift in relative abundance of the snail vectors Biomphalaria alexandrina and Bulinus truncatus. Biomphalaria is increasing while the latter has disappeared from a village in the Fayoum where formerly only schistosomiasis haematobia was endemic. A cross-sectional household survey in this village in 1991 showed the following prevalence values: S. mansoni, 22.3%; S. haematobium, 3.4%; and mixed infections, 2.8%. Only two children less than 10 years of age had S. haematobium infections. A review of the local Ministry of Health records showed that 1) both species were parasitologically diagnosed during the past 7.5 years, 2) Biomphalaria had been abundantly present in the local waterways for the past 10 years and has been found infected with S. mansoni since 1985, 3) Bulinus has not been detected in the local canals and drains since 1986 and the few found between 1981 and 1985 were not infected, and 4) Biomphalaria in this village and in two others in the Fayoum were believed infected by laborers from the Delta who helped build schools in 1984. This change in the distribution of schistosomiasis will impact upon public health and medical practice in Middle and Upper Egypt as it already has in Lower Egypt.

Therapeutic advances in ulcerative colitis.

Ulcerative colitis is an inflammatory condition that requires individualized and innovative therapy for each patient depending on the symptoms, location, severity, and chronicity of the disease. It is most often a chronic illness that requires modification in treatment as the stage of the disease changes. Systemic and rectal aminosalicylates (sulfasalazine, mesalamine, olsalazine and corticosteroids) remain the most useful therapeutic agents. Rectally administered mesalamine and the forms of oral mesalamine appear to have significant advantage over sulfasalazine dosage forms. Future clinical usage and scientific study will determine the place of these newer agents among other medical therapies and the surgical management of ulcerative colitis.

Studies on liver profile after prolonged praziquantel courses for schistosomiasis mansoni in Egyptian children on a field level.

The effect of prolonged praziquantel courses on the clinical, sonographic and functional aspects of the liver in bilharzial and nonbilharzial school-children on village level was investigated in this study. Bilharzial--positive school--children were divided into three groups according to Praziquantel regimes. Each case received an initial dose of 40 mg/Kg. PZQ. Subsequently the first group received 6-monthly full dose, the second group received 3-monthly half doses and the third group received monthly half doses. Another 3 groups of bilharzial negative children were used as a control receiving oral vitamin B complex as placebo. Clinico-parasitological and sonographic examinations as well as liver function tests were done before and after drug administration. It was concluded according to our results that healing of hepatic pathology was slower than parasitological cure. Moreover complete reversibility of hepatic size required frequent praziquantel doses (from 3 to 7). Hepatic healing is dose related. Less doses are required for parasitological cure.

Progress in the control of schistosomiasis in Egypt 1985-1988.

Continuing epidemiological evaluation of schistosomiasis intervention measures applied in Middle and Upper Egypt since 1985 indicate that a large measure of control of Schistosoma haematobium has been achieved in relation to both prevalence and intensity of the infection and incidence of new infections. Transmission control has, however, been inadequate in many areas, since numerous re-infections occurred in treated schoolchildren. Variable compliance rates in the chemotherapy delivery system were probably, in part, an important contributory factor, and short-comings of the selective and/or focal mollusciciding strategy were also probably responsible for many new cases and re-infections. Chemotherapy delivery has now been improved following the introduction of single dose treatments with praziquantel and it is expected that there will be an increased demand for treatment following the introduction of a new information-education-communication campaign. In communities with geometric mean egg-output of less than 50 per 10 ml of urine, acceptable control of the potential for development of schistosomal disease can be expected. It is concluded, therefore, that the future maintenance control strategy in this project area may call for more frequent chemotherapy treatments in identified foci of high prevalence and intensity, with complementary focal mollusciciding and/or targeted treatment of schoolchildren, in order to prevent the serious consequences of infection. In 1988 the annual cost of schistosomiasis control measures per person throughout the project area (2 million irrigated feddans (c .800,000 hectares] containing 12 million people) was 0.5 Egyptian pounds (LE) (US$ 0.20), representing 5.2% of the annual expenditure per person in Egypt (LE 9.6) for all health services.

1983 Nile Delta schistosomiasis survey: 48 years after Scott.

To determine whether the sharply declining Schistosoma haematobium infection rates in parts of the Nile Delta could be generalized to the entire region, and to update the status of S. mansoni infection rates, a large scale survey was undertaken in 1983 in 70 of the 71 districts of the Nile Delta. In a house-to-house survey, greater than 91% of the sample population of 16,675 participated by providing stool and/or urine specimens which were examined qualitatively by Kato thick smear and sedimentation techniques, respectively. After the 1935 survey by Scott, the prevalence of S. mansoni appeared to change little, from 33% in 1935 to 39% in 1983, but a more sensitive diagnostic technique in 1983 strongly suggested that the actual prevalence had decreased between the 2 surveys. In contrast, the prevalence of S. haematobium infection decreased from 56% to 5%, with a similar decline in all 8 governorates. The dramatic decline in S. haematobium prevalence has been accompanied temporally with a sharp decrease in the population density of Bulinus truncatus. S. mansoni has become the predominant human schistosome species in the Nile Delta.

Emergency-room services for a community health center.

The development and maintenance of an organized system of emergency care in isolated ambulatory health-care centers are described. A system of three community health centers, staffed chiefly by midlevel practitioners (i.e., physician's associates and nurse practitioners), had a need to provide occasional emergency care to patients. Emergency care needed to be provided (for up to one hour) until an ambulance arrived to transport the patient to a hospital. A system of emergency care, consisting of treatment protocols, a drug manual, equipment and medications, and a program for periodic inservice education was developed by physicians, midlevel practitioners, and pharmacists. Weekly checks of the supplies and medications are conducted. Lists of supplies and medications stocked, and a sample drug monograph, are included in the paper. The program has resulted in more efficient emergency care, including less confusion in executing and documenting treatment.