Background
Descriptions of cutaneous findings associated with COVID‐19 have not been consistently accompanied by histopathology or confirmatory testing for SARS‐CoV‐2.
Objective
To describe and ...classify the cutaneous findings with supporting histopathology of confirmed COVID‐19 inpatients.
Methods
We included consecutive inpatients with a confirmed diagnosis of COVID‐19 for whom a dermatology consult was requested. A skin biopsy was performed in all cases. Skin findings were classified as being compatible with a cutaneous manifestation of COVID‐19 or as representing a distinct clinical entity.
Results
Twenty‐eight patients were studied in whom thirty‐one dermatologic diagnoses were made. Twenty‐two of the dermatoses were compatible with a cutaneous manifestation of COVID‐19; nine entities were not associated with infection by SARS‐CoV‐2. The most common COVID‐19‐associated pattern was an exanthematous presentation. In four patients, a new pattern was observed, characterized by discrete papules with varied histopathological findings including a case of neutrophilic eccrine hidradenitis. No cases of pernio‐like lesions were identified. Skin findings not associated with COVID‐19 represented 29% of diagnoses and included Malassezia folliculitis, tinea, miliaria and contact dermatitis.
Limitations
There is no gold‐standard test to distinguish between viral exanthems and drug reactions.
Conclusion
A histopathological study is critical before attributing skin findings to a manifestation of COVID‐19.
Linked Commentary: F. Rongioletti. J Eur Acad Dermatol Venereol 2021; 35: 1742–1743. https://doi.org/10.1111/jdv.17414.
•First description of extended-spectrum β-lactamase CTX-M-15 in Haemophilus parainfluenzae.•H. parainfluenzae is a potential reservoir of resistance genes.•Increasing prevalence of urogenital ...infections caused by H. parainfluenzae.•H. parainfluenzae may be a causative agent of sexually-transmitted infections (STIs).•H. parainfluenzae might transmit resistance determinants to other STI-associated pathogens.
Haemophilus parainfluenzae is a commensal organism with rising numbers of multidrug-resistant (MDR) strains. This pathogen is of increasing clinical relevance in urogenital infection. The aim of this work was to identify and characterise the molecular mechanisms of resistance associated with four cephalosporin-resistant H. parainfluenzae strains collected from patients with urethritis. Antimicrobial resistance was determined by microdilution following European Committee on Antimicrobial Susceptibility Testing criteria. Strains were then analysed by whole-genome sequencing to determine clonal relationship and the molecular basis of antimicrobial resistance. Finally, a phylogenetic analysis was performed on all urogenital MDR strains of H. parainfluenzae previously isolated in our hospital. All strains were resistant to β-lactams, macrolides, tetracycline, fluoroquinolones, chloramphenicol, cotrimoxazole, and aminoglycosides. The resistance profile was compatible with the presence of an extended-spectrum β-lactamase (ESBL). Whole-genome sequencing detected blaCTX-M-15 that conferred high minimum inhibitory concentrations to cephalosporins in two novel integrative and conjugative elements (ICEHpaHUB6 and ICEHpaHUB7) that also harboured a blaTEM-1 β-lactamase. This study shows a novel blaCTX-M-15 ESBL carried in an integrative conjugative element in four extensively drug-resistant H. parainfluenzae strains. This resistance determinant could be transmitted to other sexually transmitted pathogens and this is a cause for concern.
CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy) disease is an inherited systemic arterial disease that affects the small and medium calibre ...cerebral vessels. Around 500 families are affected in the world, most of them in Europe. It is characterised by migraine attacks, subcortical dementia, neuropsychiatric disorders, and recurrent ischaemic strokes. The objective of this article is to describe, for the first time in the literature, the management by general anaesthesia of an intracranial neurosurgical procedure in a patient with CADASIL disease. Continuous monitoring of blood pressure is considered essential, as well as the maintenance of normocapnia and normothermia to avoid the development of new cerebrovascular accidents. This disease is relevant due to its anaesthetic implications and the few publications to date.
Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and ...epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18–77 years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρ = 0.7419, p < 0.0001), with median values of 1.5 mg/L and 2 μg/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55 ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15 ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (β = 0.56, p < 0.001), Cys-C (β = 0.022, p = 0.001), KIM-1 (β = 0.048, p = 0.008), OPN (β = 0.38, p = 0.041), and eGFR (β = 0.49, p = 0.03); however, CLU (β = 0.07, p = 0.100) and TFF-3 (β = 1.14, p = 0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.
•Fluoride exposure increased renal injury biomarkers (ALB, Cys-C, KIM-1 and OPN).•Fluoride could be considered an environmental kidney toxicant.•Exposure to low concentrations of arsenic does not increase kidney injury biomarkers.•Co-exposure to low arsenic level does not enhanced renal fluoride toxicity.
Abstract
Study question
Can the overall intracellular Ca2+ dynamics evoked by progesterone stimulation predict the fertilizing potential of a non-normozoospermic semen sample under fertility ...treatment?
Summary answer
Some kinetic parameters of the transient intracellular Ca2+ increase evoked by progesterone stimulation correlate with fertilization rates in conventional IVF but not with ICSI.
What is known already
Stimulation with female hormone progesterone induces the activation of the sperm-specific ion channel CatSper which in turn produces a fast increase in the intracellular Ca2+ concentration (Ca2+i). After reaching a maximum Ca2+i, different Ca2+ clearance mechanisms become active producing a transient followed by a plateau. We investigated whether the Ca2+i dynamics upon progesterone stimulus may be used to assess the fertilizing potential of sperm samples from men undergoing assisted reproduction.
Study design, size, duration
This prospective study employed unidentified semen samples from 39 non-normozoospermic men (age 38 ± 6 years old) undergoing fertility treatment from March 2022 to the present at CITMER Reproductive Medicine, Mexico City. Frozen semen samples and ART procedures with less than 3 oocytes were excluded. Ten normozoospermic semen samples were also analyzed. The progesterone-dependent Ca2+i changes were evaluated using time-lapse flow cytometry.
Participants/materials, setting, methods
Semen samples were obtained on the same day as oocyte retrieval. Sperm cells were washed and incubated in capacitating HTF media for further use in conventional IVF or ICSI procedures. When available, the surplus cells were stained with vitality and Ca2+-sensitive fluorescent dyes. Fluorescence changes were evaluated by AccuriC6 flow cytometer. Progesterone-induced Ca2+i transient as well as the correlations with the fertilization rates were calculated using custom-made R programming language code.
Main results and the role of chance
The progesterone (1 µM) stimulation evoked a fast and transitory increase in the Ca2+i. We then calculated six different kinetics parameters of such responses: basal Ca2+ level, increase and decrease in velocity, maximum Ca2+ level, total response duration, and the area under the curve (AUC). There were no significant differences in any of these parameters between normozoospermic donors (and non-normozoospermic patients. The former group of semen samples were divided into either conventional IVF (n = 17) or ICSI (n = 21). In IVF but not ICSI samples, the duration, and the area under the curve of the progesterone response tended to be higher than in normozoospermic (2.39±0.7 min, p = 0.03, and 113±30 AUF*min, p = 0.18, respectively). Furthermore, both parameters showed a tendency to correlate negatively with the conventional IVF (R= –0.45, p = 0.07 and R= –0. 5, p = 0.04, respectively) but not with ICSI fertilization ratio (number of zygotes/total number of mature oocytes). These results suggest that cells with a better Ca2+ recovery mechanism are well suited for IVF. Interestingly, we observed no difference between the magnitude of the Ca2+i increase after progesterone stimulus among donors, IVF, or ICSI samples, as was previously reported. Differences in the concentration of progesterone could explain such results.
Limitations, reasons for caution
The preliminary nature of the results implies a necessity to increase the number of analyzed semen samples (in progress). It is well known that progesterone induces variable responses even among the same donor cells. Our population-based analysis may be underestimating such single cells variations.
Wider implications of the findings
Current protocols for sperm analysis fail to successfully predict the fertilizing capability of semen samples from men seeking reproductive treatment. Further research into the molecular regulation of Ca2+ dynamics could offer promising alternatives for clinicians to appropriately choose between IVF and ICSI for each couple.
Trial registration number
.
Abstract Study question Does measuring qualitative changes in the sperm pHi could predict the fertilizing potential of a non-normozoospermic patients under fertility treatment? Summary answer The ...increase of pHi correlates with fertilization rates. What is known already The intracellular pHi (pHi) is of great importance for a wide variety of sperm physiological processes, including its motility. The pHi regulates several key sperm proteins, such as the Ca2+ channel, CatSper (sperm cation channel) which is involved in sperm hyperactivation and the K+ channel SLO3.The latter participates in the regulation of membrane potential during capacitation. Interestingly, human sperm pHi has been found to positively correlate with both hyperactivated motility and in vitro fertilization (IVF) success in normozoospermic patients. Study design, size, duration This prospective study employed unidentified semen samples from 62 non-normozoospermic men (patients, age 38 ± 4 years old) undergoing fertility treatment from January to November 2023 at CITMER Reproductive Medicine, Mexico City. Frozen semen samples and procedures with less than 4 oocytes were excluded. The pHi of sperm samples was evaluated by time-lapse flow cytometry. For comparison, the pHi of 13 normozoospermic men (donors, age 28 + 6 years old) were also analyzed. Participants/materials, setting, methods Sperm were separated by density gradient and incubated in capacitating HTF media to be used for conventional IVF or ICSI. Cells were stained with vitality (propidium iodide) and pHi (BCECF-AM) sensitive fluorescent dyes. Fluorescence changes were evaluated using an AccuriC6 flow cytometer. For each pHi recording, 10 mM NH4Cl were used as an alkalinization positive control and for data normalization. Basal levels of sperm pHi and its correlation with fertilization rates, were performed using R. Main results and the role of chance The changes in pHi were recorded as changes in the BCECF fluorescence. The increase in fluorescence is proportional to an increase in pHi and vice versa. Interestingly, we observed that the increase in pHi in sperm used for ICSI but not for IVF procedures, which were paired with oocytes from female donors, are positively and significantly correlated with higher fertilization rates (R = 0.68; *p=0.02). This seems to be the same for ICSI treatment pairing sperm with oocyte from the female partner, although the correlation is not yet statistically significant (R = 0.44; p = 0.12). We did not find significant differences in the basal pHi values between sperm from donors and patients; however, we observed that sperm from patients, had higher pHi values (0.57 + 0.15 a.u.f) compared to sperm from donors (0.48 + 0.24 a.u.f). Our results suggest that sperm pHi may be an important regulator for the process of fusion and not only for fertilization. Qualitative sperm pHi values can contribute to predicting fertilization success in patients undergoing ICSI treatment. Limitations, reasons for caution The preliminary nature of the results implies a necessity to increase the number of analyzed semen samples. Physiological responses may vary even among the same patient or cell’s donor. Our population-based analysis could be underestimating such single cell variations. Wider implications of the findings Current protocols for sperm analysis fail to successfully predict the fertilizing capacity of semen samplest.Measuring pHi in capacitated sperm, could be a promising tool to help clinicians choose the best fertilization technique for each couple. This protocol is easy to perform in a laboratory that has a flow cytometer. Trial registration number Not applicable
The Southern Chiapas focus of onchocerciasis in Southern Mexico represents one of the major onchocerciasis foci in Latin America. All 559 endemic communities of this focus have undergone semi-annual ...mass treatment with ivermectin since 1998. In 50 communities of this focus, ivermectin frequency shifted from twice to four times a year in 2003; an additional 113 communities were added to the quarterly treatment regimen in 2009 to achieve a rapid suppression of transmission.
In-depth epidemiologic and entomologic assessments were performed in six sentinel communities (which had undergone 2 rounds of ivermectin treatment per year) and three extra-sentinel communities (which had undergone 4 rounds of ivermectin treatment per year). None of the 67,924 Simulium ochraceum s.l. collected from this focus during the dry season of 2011 were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.06/2,000 flies examined. Serological assays testing for Onchocerca volvulus exposure conducted on 4,230 children 5 years of age and under (of a total population of 10,280 in this age group) revealed that 2/4,230 individuals were exposed to O. volvulus (0.05%; one sided 95% confidence interval = 0.08%).
The in-depth epidemiological and entomological findings from the Southern Chiapas focus meet the criteria for interruption of transmission developed by the international community.
Abstract
Study question
Does the change in intracellular calcium levels evoked by artificial membrane depolarizations predict fertilization success in a non-normozoospermic semen sample undergoing ...assisted reproductive techniques?
Summary answer
The increase in the intracellular calcium after artificial plasma membrane depolarization correlates negatively with fertilization rates in conventional IVF but not with ICSI
What is known already
Sperm capacitation-related features, like the regulation of the intracellular calcium concentration (Ca2+i) and the hyperpolarization of the plasma membrane potential (Vm), have been proposed as predictors of success during artificial reproduction techniques (ART). Intriguingly, upon Vm depolarization, sperm exhibit a rapid and transitory increase in the Ca2+i controlled, likely, by the activation of the sperm-specific calcium channel CatSper. The regulation of CatSper activity is essential for sperm function and is crucial for fertilization. Therefore we wondered if the Vm depolarization-dependent rise in the Ca2+i can be used to predict fertilization success rates in non-normozoospermic semen samples of men undergoing ART.
Study design, size, duration
This prospective study employed unidentified semen samples from 29 non-normozoospermic men (37.8 ± 5.6 years old) undergoing fertility treatment from March 2022 to the present at CITMER Reproductive Medicine, Mexico City. Frozen semen samples and procedures with less than 3 oocytes were excluded. Ten normozoospermic semen samples were analyzed as a control. The depolarization-dependent Ca2+i changes were evaluated by flow cytometry under four different Vm conditions: resting (variable among samples), –64, –46, and –32 mV.
Participants/materials, setting, methods
Semen samples were obtained on the same day as oocyte retrieval. Sperm cells were washed and incubated in capacitating HTF media for further use in conventional IVF or ICSI procedures. When available, the surplus cells were stained with vitality, Ca2+, and Vm-sensitive fluorescent dyes. Fluorescence changes were evaluated by AccuriC6 flow cytometer. The kinetical analysis of the transitory Ca2+i increase as well as the statistical comparisons were performed using custom-made R programming language code.
Main results and the role of chance
Analysis of resting Vm showed that normozoospermic semen samples presented more depolarized Vm than non-normozoospermic controls (–75.7 ± 6.9 vs –67.3 ± 10.5 mV, respectively, p = 0.02). The former group of semen samples was either used for conventional IVF (n = 11) or ICSI (n = 14). The semen samples in these last categories showed a tendency to present a more depolarized Vm than non-normozoospermic samples (–69.9 ± 8.8 and –66.6 ± 11.3 mV, respectively). No differences were seen in the resting Ca2+ levels. We then induced a Vm hyperpolarization by adding the K+ ionophore, valinomycin followed by increasing concentrations of extracellular K+. Each depolarizing stimulus evoked a fast and transitory increase in the Ca2+i. We then calculated seven different kinetic parameters of such responses: basal Ca2+ level, increase and decrease velocity, maximum Ca2+ reached, response durability, and area under the curve (AUC). The basal Ca2+ level reached after depolarizing stimuli correlated negatively (R = –0.64, p = 0.03) with the conventional IVF fertilization ratio (number of zygotes/total number of mature oocytes) when the Vm was clamped either to –64 and –46 mV. A negative and significant correlation (R = –0.76, p = 0.006) was seen for the AUC analysis at –64 mV. No relevant correlations were found in the ICSI samples.
Limitations, reasons for caution
This is an in vitro study, and caution must be taken when extrapolating these results in vivo. The preliminary nature of the results implies a necessity to increase the number of analyzed semen samples (in progress).
Wider implications of the findings
Further research into the molecular regulation of the CatSper channel could offer promising alternatives for clinicians to appropriately choose between IVF and ICSI for each couple. This protocol is fast and simple to perform in a laboratory equipped with a flow cytometer or any fluorescence-based reader.
Trial registration number
NA
We measure the lifetime of the $D_s^+$ meson using a data sample of 207 fb$^{-1}$ collected by the Belle II experiment running at the SuperKEKB asymmetric-energy $e^+ e^-$ collider. The lifetime is ...determined by fitting the decay-time distribution of a sample of $116\times 10^3$ $D_s^+\rightarrow\phi\pi^+$ decays. Our result is $\tau^{}_{D^+_s} = (498.7\pm 1.7\,^{+1.1}_{-0.8})$ fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.
PDF
