Obesity in late adolescence and incident type 1 diabetes in young adulthood.

AIMS/HYPOTHESIS: Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood. METHODS: All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia. Data were linked with information about adult onset of type 1 diabetes in the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied, with BMI being analysed both as a categorical and as a continuous variable. RESULTS: There were 777 incident cases of type 1 diabetes during 15,819,750 person-years (mean age at diagnosis 25.2±3.9 years). BMI was associated with incident type 1 diabetes. In a multivariable model adjusted for age, sex and sociodemographic variables, the HRs for type 1 diabetes were 1.05 (95% CI 0.87, 1.27) for the 50th-74th BMI percentiles, 1.41 (95% CI 1.11, 1.78) for the 75th-84th BMI percentiles, 1.54 (95% CI 1.23, 1.94) for adolescents who were overweight (85th-94th percentiles), and 2.05 (95% CI 1.58, 2.66) for adolescents with obesity (≥95th percentile) (reference group: 5th-49th BMI percentiles). One increment in BMI SD was associated with a 25% greater risk for incidence of type 1 diabetes (HR 1.25, 95% CI 1.17, 1.32). CONCLUSIONS: Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

Medaka follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh): Developmental profiles of pituitary protein and gene expression levels.

The two gonadotropins follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) are of particular importance within the hypothalamic-pituitary-gonadal (HPG) axis of vertebrates. In the current study, we demonstrate the production and validation of Japanese medaka (Oryzias latipes) recombinant (md) gonadotropins Fshß (mdFshß), Lhß (mdLhß), Fshßα (mdFshßα), and Lhßα (mdLhßα) by Pichia pastoris, the generation of specific rabbit antibodies against their respective ß subunits, and their use within the development and validation of competitive enzyme-linked immunosorbent assays (ELISAs) for quantification of medaka Fsh and Lh. mdFsh and mdLh were produced as single-chain polypeptides by linking the α subunit with mdFshß or mdLhß mature protein coding sequences to produce a "tethered" polypeptide with the ß-chain at the N-terminal and the α-chain at the C-terminal. The specificity of the antibodies raised against mdFshß and mdLhß was determined by immunofluorescence (IF) for Fshß and Lhß on medaka pituitary tissue, while comparison with fluorescence in situ hybridization (FISH) for fshb and lhb mRNA was used for validation. Competitive ELISAs were developed using antibodies against mdFshß or mdLhß, and the tethered proteins mdFshßα or mdLhßα for standard curves. The standard curve for the Fsh ELISA ranged from 97.6 pg/ml to 50 ng/ml, and for the Lh ELISA from 12.21 pg/ml to 6.25 ng/ml. The sensitivity of the assays for Fsh and Lh was 44.7 and 70.8 pg/ml, respectively. A profile of pituitary protein levels of medaka Fsh and Lh comparing juveniles with adults showed significant increase of protein amount from juvenile group (body length from 12 mm to 16.5 mm) to adult group (body length from 21 mm to 26.5 mm) for both hormones in male medaka. Comparing these data to a developmental profile of pituitary mRNA expression of medaka fshb and lhb, the mRNA expression of lhb also increased during male maturation and a linear regression analysis revealed a significant increase of lhb expression with increased body length that proposes a linear model. However, fshb mRNA expression did not change significantly during male development and therefore was not correlated with body length. In summary, we have developed and validated homologous ELISA assays for medaka Fsh and Lh based on proteins produced in P. pastoris, assays that will be used to study the functions and regulations of Fsh and Lh in more detail.

The impact of preoperative breast MRI on the therapeutic management of breast cancer patients.

BACKGROUND: The role of preoperative breast MRI to evaluate the extent of disease in breast cancer patients is considered controversial. We aimed at assessing the effect of breast MRI on the management of newly diagnosed breast cancer. MATERIALS: A retrospective review of 202 consecutively seen patients who were newly diagnosed with breast cancer and who underwent preoperative breast MRIs at Assuta Ashdod between June 1, 2017, and June 1, 2020. Data included discovering suspicious lesions by conventional imaging, MRI findings, and surgical pathology results. This was analyzed to determine whether the MRI changed the management and whether it had a justified or unjustified effect on the treatment. RESULTS: The mean age was 54.51 (standard deviation, 11.34 years). Breast MRI revealed additional findings in 56 % of patients and modified therapeutic management in 32 % of the cases evaluated, having a justified effect in 87.6 %. Patients with changed management had a statistically significantly higher mastectomy rate (36 %) than those who did not (14 %). No statistically significant association was found between independent variables such as breast density, tumor location on the breast, type of tumor, patient's demographic information, etc. And whether MRI findings changed the initial treatment plan. CONCLUSIONS: MRI played an essential role in the preoperative staging of breast cancer in our study, modifying therapeutic planning in approximately one-third of the cases and having a justified effect on most of them. We, therefore, support preoperative breast MRI in newly diagnosed breast cancer patients.

Prevalence of gunshot residue particles on back seats of police vehicles.

The presence of gunshot residue (GSR) in a sample can provide valuable information in forensic investigations by associating a suspect with a shooting incident. However, in order to have confidence in the integrity of the results' interpretation, the possibility of contamination by secondary transfer of GSR occurring during the transportation of a person under custody in a police vehicle should be evaluated. In order to investigate police vehicles as a source for secondary transfer of GSR particles, a total of 51 samples were collected from the rear seats of random police vehicles and used to transport arrested individuals. Results indicated that the type of upholstery of the seats plays a main role in determining the potential for secondary GSR contamination. The potential chance of coming into contact with GSR particles in police vehicles is low. GSR contamination from police vehicles is, maybe, not of a major concern but should be taken into consideration mainly when very few characteristic GSR particles are found on an analyzed sample.

The association between phosphate level at admission and early mortality in acute pancreatitis.

BACKGROUND: Abnormal phosphate levels are associated with adverse outcomes in critical illness. However, there is scarce evidence on phosphate's impact on acute pancreatitis outcomes, and the few studies examining this subject are relatively small and show conflicting data. We sought to determine the association between phosphate level at admission and the clinical course and outcomes of acute pancreatitis. METHODS: In this retrospective single-center observational study, we included all adult patients admitted with a primary diagnosis of acute pancreatitis between January 2008 and June 2021. Phosphate levels at admission were classified as normal (2.8-4.5 mg/dl), low (below 2.8 mg/dl), or high (above 4.5 mg/dl). RESULTS: Out of 2308 cases, 1868 patients had documented phosphate levels at admission and were thus included in our final analysis. 1096 (59%) had normal phosphate levels, 686 (37%) had hypophosphatemia, and 86 (4.6%) had hyperphosphatemia on admission. 30-day mortality rates were 3.4%, 3.8%, and 19% in normal, low, and high phosphate levels, respectively. In univariate analysis, hyperphosphatemia was significantly associated with 30-day mortality, with an OR of 6.54 (95% CI 3.39-12.2, p < 0.001; AUC = 0.58). In a multivariate analysis adjusting for age, MAP, GFR, BUN, and pH, hyperphosphatemia remained a statistically significant independent predictor of early mortality (OR-2.93, 95% CI 1.28-6.51, p = 0.009). Hypophosphatemia was not significantly associated with 30-day mortality in univariate analysis, OR of 1.13 (95% CI 0.67-1.87, p = 0.6). CONCLUSION: Hyperphosphatemia at admission was independently associated with increased 30-day mortality in patients with acute pancreatitis. Hypophosphatemia at admission was not significantly associated with 30-day mortality.

Digitally processing an image of a shoe impression in blood.

Shoeprints are valuable crime scene exhibits because, given a reasonable-quality impression and a suspect shoe, the forensic investigator can correlate the impression with the shoe and pin down a suspect. In similarity to bloody fingerprints, a common practice with bloody shoeprints is that the crime scene investigator photographs the impressions at a 90° angle with a scale, develops them with amido Black, and then photographs again. In most cases, the post-development prints will feature better and more details that are usually sufficient to perform a comparison between the impression found at the crime scene and suspect's shoes. This study examined shoeprints in blood that had been collected in an apartment in northern Israel where two bodies were found. The floor tiles in the apartment had featured a colored design which in the post-development photographs of the shoeprints blended in with the blood on the floor. As a result, the shoeprint impression was partial and small details were masked. In the laboratory, we processed the pre-amido Black photograph in several steps designed to increase contrast. The result of this digital processing was a full shoeprint sufficiently clear to display randomly acquired characteristics of the sole and subsequently establish identification between the impression found at the crime scene and suspect's shoes. When chemical amplification is not sufficient, it is worth exploring other methods before proceeding with the comparison, as it is sometimes still possible to extract information from the same data using alternative methods in order to achieve a conclusive result.

A novel method for linking between a 3D printer and printed objects using toolmark comparison techniques.

Rapid advances and decreased production costs in 3D printing (3DP) have resulted in its accelerated implementation in criminal activities. Fused Deposition Modeling (FDM (3DP and Polylactic Acid (PLA) filament were chosen for the current research because they are widely used in commodity 3DP, particularly in documented criminal activities. This study shows how specific features of 3DP along with classical toolmark comparison techniques using Stereo-Microscopy and Comparison Microscopy can be used to link between two 3DP objects as well as between a printed object and a suspected 3D printer. Links are determined based on random fine marks found on the 3DP's heated stage (bed) that are replicated to the base face of the printed object. Melted filament that extrudes from the nozzle of the FDM 3DP constructs the base face of the printed object. This melted filament functions as a "casting material" after it cools down and solidifies, enabling replication of the fine marks. The observed resolution of these marks is as high as the resolution of casting material dedicated for toolmark replications. Overall, this study demonstrates a novel forensic method based on toolmark comparison for linking between a 3D printer and its printed objects.

Friction Marks of Stabbing Tools in Tires.

When receiving a stabbed tire for examination, forensic toolmark examiners can determine whether a suspect tool was used in a specific crime based on class-characteristics and individual-characteristics marks that have been left by the tool on the tire. This study discusses friction marks and their forensic value during the examination of a punctured tire. The term friction mark refers to the noticeable mark around the penetration area on a tire's surface. Tires designed to create high friction when contacting a road. Due to this design, friction is created between the stabbing tool shank and the sides of the hole. As a result of this friction, the shank of the stabbing tool wears the outer layer of tire around the hole. This leaves a friction mark whose general shape reflects the cross-sectional shape of the stabbing tool's shank. This phenomenon was observed and named by Locke (7) in his evaluation of tire puncture marks with knives. This article demonstrates the same phenomenon with other types of stabbing tools. Test stabs were produced with different tools representing a variety of cross-sectional shapes of shanks, and the resulting friction marks were photo-documented and discussed. Correlations between the various cross-sectional shapes and their corresponding friction marks are shown. Based on friction mark examination, the examiner: (i) can infer suspect tool shank cross-sectional shape with the evaluation of the friction mark shape and (ii) can deduce the maximum dimensions of the shank. This examination simplifies and accelerates the forensic comparison procedure and the investigation time.

Using headlight patterns in vehicle recognition.

Crime scenes are frequently poorly lit, making it difficult to recognize and identify implicated vehicles that have been caught on film or photographed during incidents. This paper explores vehicle recognition capabilities in dark images, specifically as when a vehicle's headlights are on and are projecting light onto a flat vertical surface. In this study, the headlight reflection patterns of 68 vehicles were photographed and analyzed. This paper presents a method for confirming or ruling out a vehicle's make and model by its headlight pattern.

A new method for opening quartz halogen light bulbs in vehicle accident investigations.

After a car accident, it is an important forensic task to evaluate the status of the vehicle's lighting at the time of impact. In some cases, the bulb has to be opened up to allow proper examination of the high and low beam filaments. Quartz halogen pressurized bulbs are both rigid and brittle and their internal pressure makes them likelier to explode. This study aimed to develop a more elegant method of breaking halogen bulbs open that would minimize the danger of explosion and the risk of damaging the filaments in the process. As part of the study, several opening methods were tried on multiple pressurized quartz halogen bulbs, such as cutting a groove with a hacksaw or a rotary tool, using a propane torch on the bulb to cut or warm it and then cooling it rapidly. Repeated testing by several examiners has shown that the new method developed in this study is the safest and easiest compared with other established methods.

A Mixture Model for the Number of Gunshot Residues Found on Suspects' Hands.

Quantifying the strength of gunshot residue (GSR) evidence requires scientific knowledge about the number of particles expected to be found on individuals who were or were not involved in a shooting. However, controlled experiments demand expensive resources in terms of microscope time and labor, which restricts the data of most studies to only a small group of individuals. We suggest a novel method that exploits data collected routinely on suspects during the daily work of forensic laboratories. These observational data relate to both persons who were involved in a shooting and innocent individuals. We suggest a mixture approach with different models for the number of gunshot residue particles in each group and develop an iterative algorithm to estimate the probabilities of observing the evidence under the defense proposition that the suspect is innocent and under the prosecution assumption that he is not. The method is applied to data of more than 500 suspects collected by the Israel National Police Division of Identification and Forensic Science. The analysis shows that the probability of finding three or more GSR particles on the hands of innocent suspects is very small, less than 1.5 in 1000 cases. Our new method enables researchers to use data on real cases, possibly supplemented by experimental data, in order to estimate the probabilities of a given GSR finding under the defense and prosecution propositions.

Spexin and a Novel Cichlid-Specific Spexin Paralog Both Inhibit FSH and LH Through a Specific Galanin Receptor (Galr2b) in Tilapia.

Spexin (SPX) is a 14 amino acid peptide hormone that has pleiotropic functions across vertebrates, one of which is involvement in the brain-pituitary-gonad axis of fish. SPX(1) has been identified in each class of vertebrates, and a second SPX (named SPX2) has been found in some non-mammalian species. We have cloned two spexin paralogs, designated as Spx1a and Spx1b, from Nile tilapia (Oreochromis niloticus) that have varying tissue distribution patterns. Spx1b is a novel peptide only identified in cichlid fish, and is more closely related to Spx1 than Spx2 homologs as supported by phylogenetic, synteny, and functional analyses. Kisspeptin, Spx, and galanin (Gal) peptides and their corresponding kiss receptors and Gal receptors (Galrs), respectively, are evolutionarily related. Cloning of six tilapia Galrs (Galr1a, Galr1b, Galr2a, Galr2b, Galr type 1, and Galr type 2) and subsequent in vitro second-messenger reporter assays for Gαs, Gαq, and Gαi suggests that Gal and Spx activate Galr1a/Galr2a and Galr2b, respectively. A decrease in plasma follicle stimulating hormone and luteinizing hormone concentrations was observed with injections of Spx1a or Spx1b in vivo. Additionally, application of Spx1a and Spx1b to pituitary slices decreased the firing rate of LH cells, suggesting that the peptides can act directly at the level of the pituitary. These data collectively suggest an inhibitory mechanism of action against the secretion of gonadotropins for a traditional and a novel spexin paralog in cichlid species.

Establishment of specific enzyme-linked immunosorbent assay (ELISA) for measuring Fsh and Lh levels in medaka (Oryzias latipes), using recombinant gonadotropins.

The paucity of information on understanding the regulatory mechanisms that are involved in the control of piscine Fsh and Lh synthesis, secretion, and function, prompted the present work. Part of the problem is related to the molecular heterogeneity and the unavailability of Fsh and Lh assays for quantifying gonadotropins, in particular assays regarding the measurement of Fsh, and such assays are available today for only a few teleost species. The present study reports the development and validation of competitive ELISAs for quantitative determination of medaka Fsh and Lh by first producing medaka recombinant (md) gonadotropins mdFshß, mdLhß, mdFshßα, and mdLhßα by Pichia pastoris, generating specific antibodies against their respective ß subunits, and their use within the development of ELISAs. The advantages of this protocol include: •The reproducibility of the ELISA demonstrated was relatively high, as shown by reasonably low intra- (Fsh 2.7%, Lh 3%) and interassay CVs (Fsh 5.3%, Lh 5.7%).•The high degree of parallelism between serial dilutions of the recombinant and native pituitary-derived Fsh and Lh, may be a sign of similar structures and immunologically similarity.•Two new competitive ELISAs for the quantification of medaka Fsh and Lh were established for the first time.

Data on Western blot and ELISA analysis of medaka (Oryzias latipes) follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) using recombinant proteins expressed with Pichia pastoris.

The gonadotropins follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) play essential roles in vertebrate reproduction. This article presents data on molecular weight validation of recombinant medaka (Oryzias latipes) (md) gonadotropins Fshß (mdFshß), Lhß (mdLhß), Fshßα (mdFshßα), and Lhßα (mdLhßα) generated by Pichia pastoris, as well as data on a validation of produced antibodies against Fshß and Lhß by Western blot analysis. Furthermore, the article includes data on Fsh and Lh protein levels in male medaka pituitaries using recombinant mdFshßα and mdLhßα within enzyme-linked immunosorbent assays (ELISAs), in which protein amounts were analyzed related to body weight and age of the fish. This dataset is associated with the research article entitled "Medaka Follicle-stimulating hormone (Fsh) and Luteinizing hormone (Lh): Developmental profiles of pituitary protein and gene expression" (Burow et al., in press).

Dual fingerprint reagents with enhanced sensitivity: 5-methoxy- and 5-methylthioninhydrin.

"Dual fingerprint reagents" are chemical formulations which produce with latent fingerprints in a single step, impressions that are both colored and fluorescent. Pre-mixed solutions of the two commercially available ninhydrin analogues, 5-methoxyninhydrin (MN) and 5-methylthioninhydrin (MTN) with zinc or cadmium salts, are true dual reagents. They are much more sensitive than the parent dual reagent, ninhydrin/ZnCl(2). The main advantage of the new formulations is that they can be used at room temperature, with no need to cool the sample to liquid nitrogen temperature. At 0.05% concentration, which is 10-fold lower than the common ninhydrin working solution, MTN/ZnCl(2) is as sensitive as DFO in the fluorescence mode and considerably more sensitive in the color mode. MTN is also slightly cheaper than DFO.

Classification Improvements in Automated Gunshot Residue (GSR) Scans.

Classification of particles as gunshot residues (GSRs) is conducted using a semiautomatic approach in which the system first classifies particles based on an automatic elemental analysis, and then, examiners manually analyze particles having compositions which are characteristic of or consistent with GSRs. Analyzing all the particles in the second stage is time consuming with many particles classified by the initial automated system as being potentially GSRs excluded as such by the forensic examiner. In this paper, a new algorithm is developed to improve the initial classification step. The algorithm is based on a binary tree that was trained on almost 16,000 particles from 43 stubs used to sample hands of suspects. The classification algorithm was tested on 5,900 particles from 23 independent stubs and performed very well in terms of false positive and false negative rates. A routine use of the new algorithm can reduce significantly the analysis time of GSRs.

DNA profiling from heroin street dose packages.

A large amount of heroin street doses are seized and examined for drug content by the Israel police. These are generally wrapped in heat-sealed plastic. Occasionally it is possible to visualize latent fingerprints on the plastic wrap itself, but the small size of the plastic item and the sealing process makes the success rate very low. In this study, the possibility of extracting and profiling DNA from the burnt edge of the plastic wrap was investigated. The idea was based on the assumption that epithelial cells might be trapped during the sealing process. The results show that there are sufficient quantities of DNA deposited at the "amorphic" burnt edges of sealed street doses for DNA profiling to be carried out. A controlled experiment using a known donor was performed. This subject carried out sealing of "street drug" packages and consequent DNA extractions were performed to show that known DNA profiles could be recovered from such packages, as a result of handling by the "packer." "Square-like" burnt edges did not yield DNA profiles, probably because of differences in the sealing process. It was also shown that DNA could be recovered from the plastic wrap itself and not only from the amorphic burnt edges. As heroin dealers and drug users are often involved in other crimes and run-ins with the law, the effective extraction and addition of their DNA profiles from such items of evidence to the newly established DNA database in Israel provides new avenues in the continued fight against crime and drug traffickers.

Fingerprint reagents with dual action: color and fluorescence.

We define "dual fingerprint reagents" as chemical formulations that produce with latent fingerprints in one stage impressions that are both colored and fluorescent. Solutions containing ninhydrin and group IIb metal salts appear to be true dual reagents. Application of these formulations to latent fingerprints on paper is as efficient as the two-step process beginning with ninhydrin and followed by treatment with metal salt. In the color mode, fingerprint detectability with the two ninhydrin-metal salt reagents (one with zinc chloride and the other with cadmium chloride) is comparable with that of ninhydrin itself, in spite of the difference in color. The sensitivity is significantly higher in the fluorescence mode. To view the latent impressions the exhibits are treated with ninhydrin-metal salt reagents and observed under white light illumination and under fluorescence conditions. Cooling to liquid nitrogen temperature enhances the fluorescence considerably. In the shorter wavelength domain, ninhydrin-metal salt reagents exhibit higher sensitivity than the recently reported dual reagent, genipin. The latter is advantageous, however, in the longer wavelength domain, on paper items with strong self-fluorescence, such as brown wrapping paper or paper printed with fluorescent ink. Upon reduction of the ninhydrin concentration 10-fold, ninhydrin-metal salt formulations become purely fluorogenic reagents; no color is noticed but the fluorescence is as intense as with concentrated solutions. Working at lower concentrations is an advantage from ecological and economical viewpoints.

Genipin, a novel fingerprint reagent with colorimetric and fluorogenic activity, part II: optimization, scope and limitations.

Genipin, a hydrolytic product of geniposide extracted from gardenia fruit, was thoroughly studied as a potential fingerprint reagent, and optimal conditions for fingerprint development have been determined. Latent fingerprints on paper items that have been treated with a non-ink running formulation containing 0.17% of the reagent, showed up as both colored and fluorescent images. On brown wrapping paper and on papers with highly luminescent backgrounds, genipin developed more visible and clearer prints than did classical reagents such as ninhydrin or DFO. Another potential advantage of genipin is that it is totally harmless and an environmentally friendly reagent.

Genipin--a novel fingerprint reagent with colorimetric and fluorogenic activity.

Genipin, the hydrolytic product of geniposide, which is extracted from gardenia fruit, shows good potential as a fingerprint reagent. It develops latent fingerprints on paper as blue impressions with good contrast and resolution. Even very faint impressions that are barely visible in ambient light will fluoresce brightly upon illumination at ca. 590 nm and are best viewed with a barrier filter above 630 nm. Potential advantages of genipin are the combination of colorimetric and fluorogenic activity in one reagent as well as its being a safe and environmentally friendly natural product.