Comparison of aerosol generation between electrocautery and cold dissection tonsillectomy.

OBJECTIVE: Coronavirus disease 2019 can spread through aerosols produced by surgical procedures, but knowledge of the extent of aerosol production and the risk posed by many common procedures does not exist. This study analysed aerosol generation during tonsillectomy and how it differs between distinct surgical techniques and instruments. The results can be used in risk assessment during current and future pandemics and epidemics. METHOD: An optical particle sizer was used to measure particle concentrations generated during tonsillectomy from the perspectives of the surgeon and other staff. Coughing is commonly used as a reference for high-risk aerosol generation; therefore, coughing and the operating theatre's background concentration were chosen as reference values. Different instruments were also compared to find the safest way to perform the tonsillectomy from the perspective of airborne transmission. RESULTS: Eighteen tonsillectomies were evaluated; all techniques mostly generated less than 1 µm particles. For the surgeon, bipolar electrocautery significantly exceeded the particle generation of coughing in both total and less than 1 µm particles and was found to produce significantly higher total and less than 1 µm aerosol concentrations than cold dissection and BiZact. No technique exposed other staff to a greater aerosol concentration than is generated by a cough. CONCLUSION: Bipolar electrocautery generated high aerosol concentrations during tonsillectomy; cold dissection generated significantly less. The results support cold dissection as the primary tonsillectomy technique, particularly during the epidemics of airborne diseases.

Rhinological procedures result in minimal generation of aerosols.

BACKGROUND: COVID-19 and other respiratory infections spread through aerosols produced in respiratory activities and in certain surgical procedures considered as aerosol-generating procedures (AGP). Due to manipulation of the upper airway mucosa, rhinosurgery has been considered a particular risk for spread of respiratory infections. Our aim was to assess staff exposure to aerosols during common rhinosurgical procedures METHODS: Staff exposure to generated particle concentrations and size distributions between 0.3 λm and 10 λm were measured during rhinosurgery using an optical particle sizer without any additional collection methods. Similarly measured aerosol exposure during coughing (a commonly used risk reference for aerosol generation) and the operating room’s background concentration were chosen as reference values. RESULTS: Altogether 16 common rhinological surgeries (septoplasties and endoscopic sinus surgery) were measured. The use of suction produced significantly lower aerosol concentration compared to coughing. Low aerosol generation was observed during injection anaesthesia of the nasal mucosa. Instrument comparison revealed that the microdebrider produced fewer aerosols than cold dissection in particles of 1-5 λm and >5 λm. CONCLUSIONS: Common rhinosurgeries do not seem to generate as high aerosol concentration exposures as previously believed. Rather, the observed aerosol exposure is lower or similar to exposures during coughing. Therefore, the classification of common rhinosurgeries as AGPs should be re-assessed or possibly discarded.

Aerosol generation during coughing: an observational study.

OBJECTIVE: Coronavirus disease 2019 has highlighted the lack of knowledge on aerosol exposure during respiratory activity and aerosol-generating procedures. This study sought to determine the aerosol concentrations generated by coughing to better understand, and to set a standard for studying, aerosols generated in medical procedures. METHODS: Aerosol exposure during coughing was measured in 37 healthy volunteers in the operating theatre with an optical particle sizer, from 40 cm, 70 cm and 100 cm distances. RESULTS: Altogether, 306 volitional and 15 involuntary coughs were measured. No differences between groups were observed. CONCLUSION: Many medical procedures are expected to generate aerosols; it is unclear whether they are higher risk than normal respiratory activity. The measured aerosol exposure can be used to determine the risk for significant aerosol generation during medical procedures. Considerable variation of aerosol generation during cough was observed between individuals, but whether cough was volitional or involuntary made no difference to aerosol production.

Melanocortin-3-receptor gene variants in morbid obesity.

BACKGROUND: Linkage and knock-out mice studies suggest that the melanocortin-3-receptor (MC3R) is a candidate gene for obesity. OBJECTIVE: To evaluate whether MC3R mutations underlie morbid obesity. SUBJECTS AND METHODS: MC3R coding and 5(')-flanking regions were sequenced in 48 subjects and the detected variants genotyped in 252 morbidly obese (BMI>/=40 kg/m(2)) Finns. Gel shifts were used to examine whether a mutation in the putative promoter alters GATA-factor binding. RESULTS: Three common MC3R variants were found: a 17C>A variant, changing Thr6-->Lys in 16%, a 241G>A variant changing Val81-->Ile in 15%, and a -239A>G substitution in the GATA binding site in 21% of the subjects. Four other variants were detected in the 5(') flanking region. Frequencies of the three common variants did not differ between obese and contol subjects. Among the obese, the 17C>A and 241G>A variants were coinherited and associated with increased insulin-glucose ratios (P<0.05) and leptin levels (P<0.05). GATA-4 bound efficiently to wild type oligonucleotide, but only weakly to the oligonucleotide with the -239A>G mutation. CONCLUSIONS: MC3R gene variants are common and do not explain human morbid obesity. These variants associated with subtle changes in onset of weight gain, hyperleptinemia and insulin-glucose ratios. The -239A>G mutation abolishes binding of GATA-4 to the MC3R promoter region.

No evidence for mutations of the leptin or leptin receptor genes in women with polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is often associated with obesity and insulin resistance, both of which are features that are linked to the leptin and leptin receptor (LEPR) genes. Analysis of the leptin gene by sequencing samples from 38 well-characterized patients with PCOS revealed no mutations of the coding exons. In single-stranded conformational polymorphism (SSCP) analysis and subsequent sequencing of the LEPR gene revealed previously identified amino acid variants in exons 2, 4 and 12 as well as the pentanucleotide insertion in the 3'-untranslated region (3'-UTR). The allele frequencies of these polymorphisms did not differ from those in the general population, as assessed in 122 female controls. Compared with non-carriers, serum insulin concentrations tended to be lower in the carriers of the variant LEPR exon 12 allele as well as in the carriers of the variant LEPR 3'-UTR allele, a marker previously suggested to be associated with serum insulin concentrations. In conclusion, PCOS is not commonly a consequence of mutations of the leptin or LEPR genes. However, our data support the hypothesis that variations in the LEPR gene locus have an effect on insulin regulation.

Genome-wide scan of obesity in Finnish sibpairs reveals linkage to chromosome Xq24.

Obesity is a multifactorial trait with evidence of a genetic component. Obesity is very common in all westernized countries, including Finland, where 10% of the adult population has a body mass index of 32 kg/m2 or more. Here we report results from a three-stage genome-wide scan of obesity in 188 affected subjects (body mass index, > or =32 kg/m2) from 87 Finnish families. Initially, 374 markers with an average density of 10 centimorgans were genotyped. The strongest evidence for linkage to obesity was detected on chromosome Xq24, with the marker DXS6804 providing a maximum likelihood score (MLS) 3.14 in a model-free 2-point sibpair analysis. Fine-mapping in an extended sample set of 367 affected subjects from 166 families yielded a multipoint MLS of 3.48 over this X-chromosomal region. The Xq24 region contains a plausible candidate gene, serotonin 2C receptor, variants of which have been shown to predispose to obesity and type II diabetes in mice. Another chromosomal region also provided suggestive evidence of linkage, an area on 18q21, flanking the melanocortin-4 receptor, where a 2-point MLS of 2.42 with marker D18S1155 was obtained with a set of 367 affected subjects. In conclusion, our results in this Finnish study sample suggest that a locus on chromosome Xq24 influences the risk of obesity.

The common pentanucleotide polymorphism of the 3'-untranslated region of the leptin receptor gene is associated with serum insulin levels and the risk of type 2 diabetes in non-diabetic men: a prospective case-control study.

OBJECTIVES: The purpose of the study was to test whether the pentanucleotide insertion/deletion polymorphism in the 3'-untranslated region (3'-UTR) of the leptin receptor gene, which has previously been associated with serum insulin levels in obese subjects, is associated with insulin levels and the risk of type 2 diabetes in non-diabetic middle-aged men. SUBJECTS AND DESIGN: We studied these associations in a prospective population-based nested case-control study in 41 men who developed type 2 diabetes during 4-year follow-up and 81 controls who were matched for age, obesity, baseline glucose and insulin and other strongest risk factors. Both the cases and the controls came from a cohort of 985 men who had no diabetes at baseline. RESULTS: There was one homozygote and 22 heterozygotes for the 3'-UTR insertion allele amongst all 122 men. The carrier frequency of this allele was 9.8% amongst the cases and 23.5% amongst the controls. At baseline, the mean fasting serum insulin was 12.2 mU L-1 in the 23 men who were heterozygous or homozygous for the insertion allele and 17.1 mU L-1 in the 99 men who were homozygous for the deletion allele (P = 0.005). In a logistic regression model adjusting for four strongest non-matched predictors of type 2 diabetes, the carriers of the insertion allele had a 79% reduced risk of diabetes (OR = 0.21; 95% CI = 0.06-0.77, P = 0.019), compared with non-carriers. CONCLUSION: Our findings support the hypothesis that alterations in the leptin signalling system could contribute to serum insulin levels and the development of type 2 diabetes.

Are lemmings prey or predators?

Large oscillations in the populations of Norwegian lemmings have mystified both professional ecologists and lay public. Ecologists suspect that these oscillations are driven by a trophic mechanism: either an interaction between lemmings and their food supply, or an interaction between lemmings and their predators. If lemming cycles are indeed driven by a trophic interaction, can we tell whether lemmings act as the resource ('prey') or the consumer ('predator')? In trophic interaction models, peaks of resource density generally have a blunt, rounded shape, whereas peaks of consumer density are sharp and angular. Here we have applied several statistical tests to three lemming datasets and contrasted them with comparable data for cyclic voles. We find that vole peaks are blunt, consistent with their cycles being driven by the interaction with predators. In contrast, the shape of lemming peaks is consistent with the hypothesis that lemmings are functional predators, that is, their cycles are driven by their interaction with food plants. Our findings suggest that a single mechanism, such as interaction between rodents and predators, is unlikely to provide the 'universal' explanation of all cyclic rodent dynamics.

Competition intensity and its importance: results of field experiments with Anthoxanthum odoratum.

The effect of community productivity on competition was studied in 82 permanent plots using two removal experiments with the rhizomatous perennial grass Anthoxanthum odoratum. The removal of neighbouring plants had a positive effect on the number of shoots and total above-ground biomass of Anthoxanthum but no significant effect on mean shoot biomass. The relative competition intensity coefficient (RCI) calculated from these data showed that competition intensity increased with increasing community productivity. Similarly, the importance of competition and the difference between local maximum and local average population density increased with increasing community productivity. We concluded that for Anthoxanthum the impact of competition is greater in high-productivity areas and that competition reduces population density. No evidence was found supporting the importance of positive interactions between plants in tundra areas.

Testing of human homologues of murine obesity genes as candidate regions in Finnish obese sib pairs.

The human homologues of recently discovered murine obesity genes provide relevant candidates to study the genetic component of obesity in humans. We analysed the human counterparts to murine obesity genes ob, db, agouti, tub, melanocortin 4-receptor (MC4-R) and mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3), as well as two other chromosomal regions reported to be linked to obesity-related phenotypes in restricted populations. We found no significant evidence for linkage to any analysed loci in our total study material of 105 affected sib pairs collected from the genetically homogenous population of Finland. However, several markers on 14 cM chromosomal region flanking the MC4-R gene showed sharing of alleles identical-by-descent (IBD) more frequently than expected. A selected subset of non-diabetic obese sib pairs strengthened the P values down to 0.003 in this particular region. The smallest P value (P = 0.001) was obtained with a marker D18S487 in a subgroup containing only sib pairs with one lean and one obese parent. We therefore screened seven obese subjects included in our sib pair material for sequence changes in their MC4-R gene, but no mutations of apparent causal relationship were found. In conclusion, we could not find evidence for significant contribution of the chromosomal loci corresponding to the murine single gene obesity genes for human morbid obesity, but additional studies are still needed to clarify whether DNA alterations within or adjacent to the MC4-R gene play some role.

Functional analysis of the C(-188)A polymorphism of the human leptin promoter.

Mutational analysis of the promoter region of the leptin gene in morbidly obese Finnish subjects had revealed a previously unidentified C(-188)A polymorphism in the proximal promoter that showed a weak association with elevated serum leptin levels in obese male carriers of the variant (-188A) allele. In this study we demonstrated that neither expression of reporter gene constructs driven by wild-type (-188C) or variant (-188A) proximal promoter regions, nor assay of binding of cellular proteins reveal a genotype-related difference in promoter activity.

A common pentanucleotide polymorphism of the 3'-untranslated part of the leptin receptor gene generates a putative stem-loop motif in the mRNA and is associated with serum insulin levels in obese individuals.

OBJECTIVE: To find out whether genetic alterations of the leptin receptor gene underlie human forms of obesity. DESIGN: Among 249 morbidly obese adults (body mass index, BMI > or = 40 kg/m2), we screened 30 patients with the highest serum leptin levels for alterations of their leptin receptor gene by single-strand conformation polymorphism (SSCP) technique. SUBJECTS: 249 severely obese subjects (present or past BMI > or = 40 kg/m2) and 138 lean controls (BMI < or = 25 kg/m2). MEASUREMENTS: DNA analysis was carried out using SSCP technique, sequencing and polymerase chain reaction (PCR) followed by digestion with the restriction enzyme Rsal. Serum leptin, glucose, insulin and lipid concentrations were determined in obese subjects. RESULTS: We were able to detect a pentanucleotide insertion (CTTTA) in the 3'-untranslated region of the leptin receptor gene. The presence of this pentanucleotide insert generates a putative stem-loop structure in the mRNA. Association studies were carried out on this variant. The frequency of the insertion allele did not differ between 249 obese (12.4%) and 138 lean (12.0%) subjects. There was no association of serum leptin, glucose or lipid levels with the pentanucleotide genotype in the obese individuals. However, when subjects without medication affecting insulin or glucose levels were considered, serum insulin levels were found to be lower in the heterozygous carriers of the insertion allele (15.1 +/- 9.2 mU/l) than in the subjects homozygous for the deletion allele (21.8 +/- 13.7 mU/l, P = 0.0035). CONCLUSIONS: We were able to confirm the presence of a frequent insertion/deletion polymorphism close to the 3'-end of the leptin receptor gene. We also showed that serum insulin levels in morbidly obese subjects are associated with 3'-UTR variant genotype.

Leptin concentration in cord blood correlates with intrauterine growth.

Leptin is an adipocyte-derived peptide hormone regulating energy balance in experimental animals. Although the physiological function of leptin in humans is still unclear, its secretion is closely related to fat mass in adult humans. To examine how fetal growth correlates with leptin levels at birth, an umbilical cord venous blood sample was obtained at the delivery from 50 term newborn infants. Twenty-eight of the newborn infants had birth weights appropriate for gestational age (AGA; mean +/- SEM, 3362 +/- 90 g; relative birth weight, -0.08 +/- 0.2 SD), 9 were large for gestational age (birth weight, 4655 +/- 165 g; relative birth weight, 3.2 +/- 0.3 SD; P < 0.001 vs. AGA newborn infants), and 13 were small for gestational age (SGA; birth weight, 2385 +/- 69 g; relative birth weight, -2.2 +/- 0.08 SD; P < 0.001 vs. AGA newborn infants). Leptin concentrations were higher in large for gestational age (35.7 +/- 8.0 micrograms/L; P < 0.005), but lower in SGA (3.3 +/- 0.5 micrograms/L; P < 0.001) than in AGA infants (14.5 +/- 2.8 micrograms/L). When adjusted for differences in body weight, mean leptin levels were similar in the three newborn groups. Leptin concentration correlated closely with both absolute and relative birth weights (r = 0.71; P < 0.001 in both), with cord blood insulin concentration (r = 0.67; P < 0.001), and with placental weight (r = 0.60; P < 0.001). These data suggest that leptin is synthesized in utero, and that the circulating leptin concentration relates to the intrauterine growth pattern.

Novel polymorphism of the human ob gene promoter in lean and morbidly obese subjects.

OBJECTIVE: Leptin, the circulating product of the human ob gene, may play role in control of appetite and metabolic rate. We screened the proximal promoter area of the ob gene for mutations and common polymorphisms in order to find out whether genetic variation in the regulatory area of this gene plays a role in human obesity. DESIGN: The technique of single-strand-conformation polymorphism (SSCP) was applied to screen for the promoter area of the ob gene for genetic alterations in morbidly obese patients. SUBJECTS: A total of 249 morbidity obese (present or past body mass index [BMI] > or = 40 kg/m2) and 141 lean (BMI < or = 25 kg/m2) subjects. MEASUREMENTS: DNA analysis was carried out using a single-strand conformation polymorphism (SSCP) technique and PCR followed by digestion with the restriction enzyme BssHll. Leptin was determined by radioimmunoassay in obese subjects. Serum lipids, glucose and insulin concentrations in the obese subjects were also determined. RESULTS: A new polymorphism C(-188)A was identified in the promoter region of the ob gene. This polymorphism was detected with allelic frequencies of 0.06 in morbidly obese subjects and 0.09 in lean controls (P = 0.28). Initial studies failed to show an association of this polymorphism with serum leptin, response to treatment for obesity, history and extent of weight gain, or serum insulin, glucose of lipid concentrations. CONCLUSIONS: We have identified a common polymorphism in the promoter area of the human ob gene which appears to be very useful for genetic association and linkage studies. Further studies are needed to elucidate its potential role in the regulation of the human ob gene and in human metabolic disorders.

Estimation of individual dust exposure by magnetopneumography in stainless steel production.

The objectives of the study were to measure the magnetic dust lung burden of workers in stainless steel production by magnetopneumography (MPG) and to investigate the relationship of the results with air-borne concentrations of dust, total and hexavalent chromium as well as urinary excretion of chromium. There were 128 workers from the chromite mine, sintering plant, ferrochrome smelter, stainless steel smelting shop, cold rolling mill and welding shop in the exposed groups and five persons from the office staff in the control group. The remanent magnetic field (RMF) in the lungs was slightly elevated among workers in the ferrochromium and steel smelting shops; the levels were, however, lower than those reported for welders earlier and those observed in the welding/repair shop. Workers in the mine, concentrator and sintering plants and in the cold rolling mill exhibited remanent magnetic fields comparable to the referents. There was a relationship between the RMF and the actual urinary chromium concentration. Miners and concentrator and sintering plant workers showed retarded relaxation rate (ReR) of the remanent magnetic field. However, the RMF of the first two of these groups were low (< 0.1 nT) and this made it difficult to measure the ReR accurately. The duration of exposure correlated weakly but significantly with the relaxation rate, while smoking was not related to it.

Markers for the gene ob and serum leptin levels in human morbid obesity.

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellite markers near the ob gene and morbid obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 +/- 7 kg/m2, and 151 lean controls with a mean BMI of 22 +/- 2 kg/m2, and searched for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI > or = 32). No significant association was observed between any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected ob gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in morbidly obese patients; a carrier status for either of the two most prevalent alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects. Two of the markers (D7S2519, D7S649) showed a significant relation to the weight-losing response to a 16-week very-low-calorie dietary intervention. We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage of the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of complex disorders.

Polymorphism of the beta 3-adrenergic receptor gene in morbid obesity.

OBJECTIVE: The Trp64-->Arg allele of the beta 3-adrenergic receptor gene was recently proposed to be associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), features of insulin resistance and a tendency to gain weight. We investigated whether the Arg64 allele predisposes to severe obesity. DESIGN AND SUBJECTS: A genetic association study of 254 subjects with morbid obesity [body-mass index (BMI) > or = 40; mean 42.8 +/- 7.0] and 151 lean healthy control subjects [BMI < or = 25; mean BMI 22.3 +/- 1.9]. MEASUREMENTS: beta 3-adrenergic receptor genotyping was carried out with a solid-phase minisequencing technique. Serum lipids, glucose and insulin levels in the obese subjects were also determined. RESULTS: The frequency of the Arg64 did not significantly differ in the morbidly obese patients (9.1%) and lean controls (8.9%), nor was there any statistically significant association between the mean BMI values and the beta 3-adrenergic receptor genotype. However, obese subjects carrying the Arg64 allele developed obesity more often before the age of 15 y than those without it (P < 0.05, adjusted for multiple comparisons). The frequency of the Arg64 allele was similar in nondiabetic and diabetic patients; the mean age at the onset of NIDDM did not differ according to the beta 3-adrenergic receptor genotype. There was no significant association between the receptor genotype and the level of the serum cholesterol, HDL-cholesterol, triglyceride, glucose or insulin, nor was this polymorphism associated with the behavioural or psychopathological characteristics of the morbidly obese subjects. Response to a 16 w treatment program including a very-low calorie diet (VLCD) regimen, dietary and exercise counseling, as well as behavioural modifications, did not differ according to the genotype. CONCLUSION: Our data do not support a significant role for the codon 64 polymorphism of the beta 3-adrenergic receptor as a genetic marker of morbid obesity. Although there was an association between the Arg64 allele and an earlier onset of obesity in individuals subsequently developing morbid obesity, this allele was not associated with the actual BMI gained or response to weight-loss therapy on a hypocaloric diet.

Feeding and bedding materials as sources of microbial exposure on dairy farms.

Hay, grain, silage, and bedding are the sources of mold dust in agriculture. The aim of the present study was to evaluate the effect of different farming methods on exposure to airborne microbes. The study material comprised 50 silage, 54 hay, 47 grain, and 70 bedding samples taken on 18 farms in the beginning, middle, and end of the indoor feeding season. The modified wind-tunnel technique and six-stage impactors were used to determine the number of mesophilic bacteria, xerophilic fungi, mesophilic fungi, thermotolerant fungi, and thermophilic actinomycetes liberated from each material. Baled hay and straw liberated the largest amounts of microbes. Hay, except when dried in storage, liberated great numbers of fungal spores. The proportion of respirable airborne microbe-bearing particles was greatest in the highest concentrations. Theoretically, choosing the best possible alternative work methods could diminish exposure to microbes to one-tenth of the present level.