Search

During pregnancy, thyroid homeostasis is physiologically modified, leading to altered levels of thyrotropin (TSH): hence, the adoption of pregnancy-related, population- and method-specific reference ranges is recommended. This monocentric and retrospective study was conducted to establish local pregnancy-related reference intervals for serum TSH in singleton pregnant women using real-life clinical data.We included women who measured serum TSH during pregnancy at our Laboratory over six years, excluding pregnant women with current or past history of thyroid disease, pituitary or autoimmune diseases, use of medications known to influence thyroid function, multiple and/or pathological pregnancies, BMI30 Kg/mWe retrieved a total of 3744 TSH results. Reference limits (90% confidence intervals) for TSH (in mIU/L) are: first trimester 0.09 (0.06-0.12) - 3.16 (3.05-3.29); second trimester 0.25 (0.11-0.30) - 3.55 (3.34-3.73); third trimester 0.42 (0.15-0.48) - 3.93 (3.80-4.08).In conclusion, real-life clinical data could be used to establish or verify local reference intervals for TSH in pregnant women: this may reduce the risk of misclassification of pregnant women undergoing thyroid function testing.

Setting: A causative relationship between varicocele and impairment of semen quality has been largely investigated in the context of male infertility, although its clinical benefit remains controversial.Objective: To investigate the effect of varicocele correction on detailed morphologic microscopic semen parameters in a large homogeneous cohort of patients and to evaluate which factors could predict semen improvement after the surgical treatment.Design: An observational, retrospective cohort study was carried out including all patients undergoing surgical treatment for varicocele from September 2011 to March 2020 in the same clinical centre. Enrolled males performed at least one semen analysis before and one after surgical varicocele correction. Primary outcome was the detailed morphologic microscopic sperm evaluation. Secondary outcomes were conventional semen analyses.Results: 121 males (mean age 24.6+6.1 years) were enrolled. Using detailed morphologic microscopic sperm evaluation, a significant morphological improvement was recorded, with a reduction in head and tail abnormalities. Moreover, a significant increase in sperm concentration (p=0.015) and percentage of progressive and total motility (p=0.022 and p=0.039) were observed after surgery. The multivariate logistic analysis identified the ultrasonography varicocele degree before surgery as a main predictor of the sperm concentration improvement (p=0.016), with the highest improvement for varicocele of I and II degree. Conclusion: For the first time, the detailed morphologic microscopic sperm evaluation highlights a relevant reduction in sperm abnormalities after varicocele surgery, showing its potential application in clinical practice.

It has been hypothesized that bacille Calmette-Guerin (BCG), the anti-tuberculosis vaccine, can be protective against Covid-19. Using data of performed swabs and RT-PCR results for SARS-CoV-2 in the Reggio Emilia province (Emilia-Romagna Region, Northern Italy) from March 6th to March 26th, 2020, we computed age, gender, and place of birth (Italy or abroad) specific risk of being tested, prevalence of positive tests, and probability of testing positive given that a swab has been taken during the epidemic peak. We report that immigrants resident in Reggio Emilia province, mostly coming from Countries with high BCG vaccination coverage, and Italians had a similar prevalence of infection (odds ratio - OR 0.99; 95%CI 0.82-1.20) and similar probability of being tested (OR 0.93; 95%CI 0.81-1.10). Our data do not support the hypothesis that immigrants from Countries where BCG vaccination is recommended have a lower risk of Covid-19 infection.

In continuation of our studies on the determination of the structural features of functionalized peptides in solution by combining time-resolved fluorescence data and molecular mechanics results, the conformational properties of a series of linear, homo-Aib peptides in methanol (a structure-supporting solvent) were investigated. These compounds have the general formula P(Aib)nN, where Aib is alpha-aminoisobutyric acid, N is naphthalene and P is the monomethylated protoporphyrin IX, the two latter chromophores being covalently attached to the peptide C- and N-termini, respectively, while n=3, 6 and 9. According to 1H NMR and IR spectra, the peptides investigated largely populate a 3(10)-helical structure in CDCl3, which is also a structure-supporting solvent. Both steady-state and time-resolved fluorescence measurements show a strong quenching of the N emission that parallels an increase of the P fluorescence intensity, suggesting the occurrence of long-range energy transfer from 1N* to ground-state P. Comparison of quenching efficiencies and lifetime pre-exponents with those obtained theoretically from the deepest energy minimum conformers is very satisfactory. The computed structures, built up by partially taking into account the solvent medium, exhibit a rigid, highly compact arrangement, owing to both the 3(10)-helix conformation of the backbone chain and the very few peptide-to-chromophore covalent linkages. As a result, only one or two stable conformations for each peptide were theoretically found, in full agreement with the time-resolved fluorescence data. Orientational effects between the probes must be taken into account for a correct interpretation of the fluorescence decay results, which implies that interconversion among conformational substates of the N linkages is slower than 10 ns, corresponding to the upper limit of the energy transfer characteristic time.

In continuation of our studies on the determination of the structural features of functionalized peptides in solution by combining time-resolved fluorescence data and molecular mechanics results, the conformational features of a series of linear, L-(αMe)Val-based peptides have been investigated in methanol. These foldamers have the general formula F[(αMe)Val]r-T-[(αMe)Val]2NHtBu, where (αMe)Val = Cα-methylvaline and r = 0–3, while F [= fluoren-9-ylmethoxycarbonyl (Fmoc)] and T [= 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-carboxylic (Toac)] are a fluorophoric Nα-protecting group and a nitroxide-based α-amino acid quencher, respectively. According to ir and CD spectra, the longest term of the series (r = 3) attains a 310-helical structure, while the other peptides populate an intramolecularly H-bonded, 310-helix-like conformation affected by dynamic helical distortions, which are enhanced by the shortness of the backbone chain. Such distortions are reflected in both the energy of the stretching mode and the molar extinction coefficient of the H-bonded NH groups, the former being higher and the latter smaller than those of a stable 310-helix. Steady-state and time-resolved fluorescence measurements in methanol show a strong quenching of Fmoc by the Toac residue, located at different helix positions, depending on the r value. Comparison of quenching efficiencies and lifetime preexponents with those theoretically obtained from the deepest energy minimum conformers, assuming a Forster mechanism, is satisfactory. The computed structures exhibit a rather compact arrangement, which accounts for the few sterically favored conformations for each peptide, in full agreement with the time-resolved fluorescence data. Orientational effects between the probes must be taken into account for a correct interpretation of the fluorescence decay results, implying that interconversion among conformational substates involving the probes is slower than the energy transfer rate. © 2001 John Wiley & Sons, Inc. Biopolymers (Pept Sci) 55: 425–435, 2000

We have designed and synthesized by solution methods two simple two-helix bundles based on a conformationally constrained cyclo-dipeptide template to the side chains of which two short, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid spin-monolabeled, 310-helical peptides are covalently tethered. The preferred conformation of the appended chains has been assessed by FTIR absorption. The conclusions are corroborated by an X-ray diffraction analysis of one of the terminally blocked pentapeptide tails. For the first time, a solvent-dependent, inter-helix interaction has been monitored by conventional ESR spectroscopy on fully synthetic peptide systems. Half-field ESR measurements of these side-chain-substituted templates provided an experimental average distance between the two labels that is in good accord with that determined in a molecular modeling study.

A novel peptide-linked [Ru(bpy)3]2+−C60 dyad is shown to undergo an intramolecular photoinduced electron transfer in chlorinated hydrocarbons that causes quenching of the emission associated to the...

We have synthesized by solution methods and fully characterized the Nα-blocked heptapeptide methylamide mBrBz-[L-Iva-L-(αMe)Val]2-L-(αMe)Phe-L-(αMe)Val-L-Iva-NHMe, fully based on conformationally constrained Cα-methylated α-amino acids. An X-ray diffraction investigation of the Nα-benzyloxycarbonylated analogue showed that in the crystal state both independent molecules (A and B) in the asymmetric unit of the peptide adopt a fully developed, regular, right-handed 310-helical structure, although molecule A would be slightly distorted at the C-terminal residue. Solution conformational analysis on the mBrBz-blocked peptide was carried out in CDCl3 by means of NMR spectroscopy. For structure determination we performed restrained molecular dynamics simulations in CDCl3 based on a search of the conformational space derived from a simulated annealing strategy. For this peptide the NMR observables can be described by a single backbone conformation, more specifically a rigid 310-helix spanning the amino acid seque...

Thermal ring opening of N-[3-(triethoxysilyl)propyl]-2-carbomethoxyaziridine in the presence of C60 produces a fulleropyrrolidine derivative which is then attached covalently to HPLC silica gel. The new chromatographic material is used to investigate binding affinities of potential hosts for the immobilized C60. Exceptionally high size selectivities have been obtained for cyclic oligomeric compounds like calixarenes and cyclodextrins in organic and water-rich media, respectively. A number of rationally designed, helical-shaped peptides bind selectively to the grafted fullerene. The most tightly bound peptide carries two ferrocene moieties at the periphery of a hydrophobic binding cavity complementary in size to C60.

Terminally blocked, isotactic homopeptides from the sterically demanding α-methylvaline of general formula Y-[L-(αMe)Val]n-OtBu (Y = Z, pBrBz, Ac; n = 2–8) have been prepared step-by-step in solution and fully characterized. The conformations preferred in solution (β-turn and right-handed 310-helix) have been assessed by FT-IR, 1H NMR and CD spectroscopy. The molecular and crystal structures of the Z-protected trimer, hexamer, heptamer and octamer have been determined by X-ray diffraction. In the crystal state, while the trimer is folded in a type III β-turn conformation, the longest homopeptides form well-developed, regular, right-handed 310-helices. The screw sense in the helix of the pBrBz-blocked octamer has been confirmed to be right-handed by solid-state and solution CD spectroscopy. The possible exploitation of these peptide helices as rigid and precise molecular rulers is discussed.

For the first time a number of derivatives and terminally blocked model peptides (to the pentapeptide level) of the sterically demanding Cα-methyl-homo-phenylalanine, (αMe)Hph, residue have been synthesized (by solution methods) and fully characterized. The results of a solution conformational analysis, performed by using FTIR and 1H NMR spectroscopies, favour the conclusion that (αMe)Hph is as potent a β-turn and helix promoter as (αMe)Phe (Cα-methylphenylalanine) and (αEt)Phe (Cα-ethylphenylalanine), and more potent than the Phe parent amino acid. In addition, a CD study of Nαpara-bromobenzoylated peptides suggests that the relationship between (αMe)Hph α-carbon chirality and the prevailing screw sense of the turn and helical structures that are formed is opposite to that found for (αMe)Phe and (αEt)Phe peptides, i.e. L-amino acids give right-handed helicities. This relationship is the same as that exhibited by protein amino acids, including Phe.

Background Systematic reviews have shown that, although well prepared, the Consensus Guidelines have failed to change clinical practice. In the healthcare district of Castelnovo né Monti (Reggio Emilia, Italy), it became necessary for the GPs and Clinical Pathologists to work together to jointly define laboratory profiles. Methods Observational study with two cycles of retrospective audit on test request forms, in a primary care setting. Objectives of the study were to develop pathology-specific laboratory profiles and to increase the number of provisional diagnoses on laboratory test request forms. A Multiprofessional Multidisciplinary Inter-hospital Work Team developed pathology-specific laboratory profiles for more effective test requesting. After 8 training sessions that used a combined strategy with multifaceted interventions, the 23 General Practitioners (GPs) in the trial district (Castelnovo nè Monti) tested the profiles; the 21 GPs in the Puianello district were the control group; all GPs in both districts participated in the trial. All laboratory tests for both healthcare districts are performed at the Laboratory located in the trial district. A baseline and a 1-year audit were performed in both districts on the GPs’ request forms. Results Seven pathology-specific laboratory profiles for outpatients were developed. In the year after the first audit cycle: 1) the number of tests requested in the trial district was distinctly lower than that in the previous year, with a decrease of about 5% (p Conclusions The first audit cycle showed a significant decrease in the number of tests ordered only in the trial district. The combined strategy used in this study improved the prescriptive compliance of most of the GPs involved. The presence of the clinical pathologist is seen as an added value.

Serotype, haemolytic activity and CAMP reaction of 466 strains of Streptococcus agalactiae (269 of human origin and 197 of bovine origin) isolated in the North of Italy (Lombardia, Emilia) were evaluated.The presence of the rare serotype VII was recorded in 3 human strains and in 1 bovine isolates. In human strains serotype III (32%) was the most common followed by serotypes Ia (17.1%),V (13.8%), II (9.7%), Ib (3.7%), IV (3%),VII (1.1%); 19.6% of strains resulted nontypeable. Between bovine strains the most abundant was serotype IV (22.3%), followed by Ib and III (5.6%), II (5.1%), Ia (3.6%),V (3%) and VII (0.5%), a large number was nontypeable (54.3%). Stains belonging to serotype of VI or VIII were not observed. 43 strains were anhemolytic (15 of humane origin and 28 bovine origin) and 5 strains were CAMP-negative (2 humane and 3 bovine).

The achiral, nitroxyl-containing alpha-amino acid TOAC (TOAC = 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), in combination with the chiral alpha-amino acid C(alpha)-methyl valine [(alphaMe)Val], was used to prepare short peptides (from di- to hexa-) that induced the enantioselective oxidation of racemic 1-phenylethanol to acetophenone. The best catalyst was an N(alpha)-acylated dipeptide alkylamide with the -TOAC-(alphaMe)Val- sequence folded in a stable, intramolecularly hydrogen-bonded beta-turn conformation with large, lipophilic (hydrophobic) N- and C-terminal blocking groups. We rationalized our findings by proposing models for the diastereomeric intermediates between (R)-[and (S)]-1-phenylethanol and the catalyst Fmoc-TOAC-L-(alphaMe)Val-NHiPr, based on the X-ray diffraction structure of the latter.

Linear Aib-based hexapeptides, of the general formula Ac–Toac–(Aib)n –Trp–(Aib)r –OtBu [T(Aib)n Trp], where n + r = 4, and Toac is a nitroxide spin-labeled Cα,α-disubstituted glycine, were investigated by steady-state and time-resolved fluorescence measurements in different solvent media. A related peptide, i.e., cyclo-{Orn–[(Aib)2–Trp–(Aib)2–Z]–Asp–[(Aib)2–Toac–(Aib)2–OtBu]} [T-cyclo-Trp], was also studied by the same techniques. It is a L-Orn, L-Asp diketopiperazine template, to which two Aib-based chains are covalently attached, each one containing one chromophore only, i.e., Trp or Toac. Whatever the solvent, in the former series of peptides quenching of the excited Trp exhibits three lifetime components and proceeds on a time scale from subnanoseconds to a few nanoseconds, while in the case of the template the same process occurs entirely on the nanoscale time scale, exhibiting two lifetimes only. The ir absorption spectral patterns suggest that the backbone of the peptides examined is in the 310-helical conformation, as earlier determined by x-ray diffraction for T(Aib)3Trp in the crystal state. In all cases, the fluorescence results are satisfactorily described by a dipole–dipole interaction mechanism, in which electronic energy transfer takes place from the excited Trp to Toac, provided the mutual orientation between the fluorophore and Toac is taken into account. This implies that interconversion among conformational substates is slow on the time scale of the transfer process, allowing us to estimate the dynamics of the process. Molecular mechanics calculations coupled with time decay data made it possible to build up the most probable structures of these peptides in solution. © 2000 John Wiley & Sons, Inc. Biopoly 53: 169–181, 2000

The photophysical and structural features of a series of linear, Aib-based peptides were investigated in methanol solution. These compounds have the general formula P(Aib)nN, where Aib is α-aminois...

Vibrational and electronic circular dichroism (VCD and ECD) and Fourier transform infrared (FTIR) spectra of the homo-oligopeptide series Z-[l-(αMe)Val]n-OtBu (n = 3−8) and selected Ac-[l-(αMe)Val]n-OtBu oligomers (n = 4, 6, 8) are presented. This is the first VCD study of a complete homopeptide series formed exclusively by Cα-methylated amino acids. VCD spectra were measured for the oligomers in 2,2,2-trifluoroethanol (TFE) and CDCl3 over the amide I and amide II spectral regions (1750−1475 cm-1). These oligopeptides, irrespective of the N-terminal group, were found to indicate formation of at least a partially 310-helical conformation for main-chain lengths as short as n = 4 and a fully developed 310-helix by n = 6 at high peptide concentrations. A 310-helical conformation for the octamer is consistent with previous spectroscopic studies and crystallographic results. The ECD spectra were measured for the oligomer series in TFE and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) over the 260−190 nm region. The ...

The molecular and crystal structures of the C alpha-tetrasubstituted, delta-branched alpha-amino acid C alpha-methylhomophenylalanine, H-D-(alpha Me)Hph-OH, and three peptides (to the pentamer level), including the homotripeptide, have been determined by X-ray diffraction. The peptides are Z-L-(alpha Me)Hph-(L-Ala)2-OMe pBrBz-[D-(alpha Me)Hph]3-OtBu and Ac-(Aib)2-L-(alpha Me)Hph-(Aib)2-OtBu. All the (alpha Me)Hph residues prefer phi, psi torsion angles in the helical region of the conformational map. The two terminally blocked tripeptides adopt a beta-bend conformation stabilized by a 1