Cerebellum seems to have a role both in feeding behavior and emotion regulation; therefore, it is a region that warrants further neuroimaging studies in eating disorders, severe conditions that ...determine a significant impairment in the physical and psychological domain. The aim of this study was to examine the cerebellum intrinsic connectivity during functional magnetic resonance imaging resting state in anorexia nervosa (AN), bulimia nervosa (BN), and healthy controls (CN). Resting state brain activity was decomposed into intrinsic connectivity networks (ICNs) using group spatial independent component analysis on the resting blood oxygenation level dependent time courses of 12 AN, 12 BN, and 10 CN. We extracted the cerebellar ICN and compared it between groups. Intrinsic connectivity within the cerebellar network showed some common alterations in eating disordered compared to healthy subjects (e.g., a greater connectivity with insulae, vermis, and paravermis and a lesser connectivity with parietal lobe); AN and BN patients were characterized by some peculiar alterations in connectivity patterns (e.g., greater connectivity with the insulae in AN compared to BN, greater connectivity with anterior cingulate cortex in BN compared to AN). Our data are consistent with the presence of different alterations in the cerebellar network in AN and BN patients that could be related to psychopathologic dimensions of eating disorders.
Abstract
Study question
How successful is sperm retrieval from the testicular surface of patients with non-obstructive azoospermia (NOA) undergoing microdissection testicular sperm extraction ...(mTESE)?
Summary answer
Enough good quality sperm for ICSI could be retrieved from the testicular surface in only 33 out of 224 patients (14.7%)
What is known already
Due to the anatomic singularity of NOA, characterized by the heterogeneous distribution of histologically and functionally distinct seminiferous tubules, retrieving enough good quality sperm for ICSI may require a complete testicular dissection. While conventional TESE (cTESE) may reach only the seminiferous tubules located in the testis surface, mTESE allows the nearly complete exploration of the whole testicular parenchyma. This is the reason why mTESE provides better sperm retrieval rates compared to cTESE, according to two systematic reviews and one meta-analysis: the superiority of mTESE compared to cTESE, however, has been challenged by a recent meta-analysis.
Study design, size, duration
Retrospective cohort study on 224 patients, aged 37 (20-54) years, who underwent unilateral (71, 31.7%) or bilateral (153, 68.3%) mTESE from January 2018 through May 2021. 175 patients were naïve for mTESE, while 49 underwent a salvage mTESE following one or more previously failed conventional TESE.
Participants/materials, setting, methods
The testis was opened like a book following a transversal incision of the testis covering two-thirds to three-quarters of its circumference: the entire surface of the testicular parenchyma was explored first in search for dilated seminiferous tubules. If no/ not enough sperm were retrieved, the testis was opened till to be fully bivalve, and the deeper portion of the testicular parenchyma was explored both into hilum direction and orthogonally to the para-equatorial section plan.
Main results and the role of chance
Sperm was retrieved in 114 patients (50.8%), 67 (94.3%) undergoing unilateral and 47 (30.7%) undergoing bilateral mTESE: only 15/153 (9.8%) had their testicular sperm retrieved in the second testis following the unsuccessful sperm retrieval in the first testis, while in the remaining cases sperm had to be retrieved from both testes to obtain enough good quality sperm for ICSI. Histopathology demonstrated Sertoli-cell only syndrome in 65.6% of operated testes, while maturation arrest was found in 19.8%, hypospermatogenesis in 12.6% and hyalinosis in 1.5%. Sperm were obtained from the testis surface in 33 out of 114 patients (28.9%); in the remaining patients a deeper dissection was needed. No difference was seen among patients with sperm found in the surface or requiring deeper dissection in terms of age, testis volume, serum testosterone level, and histopathological subcategories; although serum FSH and LH level were significantly lower in patients with sperm retrieved from the testicular surface, on multivariate logistic regression they were not found to predict the chance of retrieving sperm from the surface (OR 0.96, 95% CI 0.92-1.007, p = 0.104 and OR 0.95, 95% CI 0.85-1.06, p = 0.405, respectively).
Limitations, reasons for caution
the amount of testicular tissue dissected was strictly dependent upon the chance of finding enough sperm for ICSI in the specimens handled by the biologist in the operating room: we cannot exclude that in some patients enough sperm could be obtained from the testis surface following further extensive search
Wider implications of the findings
mTESE is to be preferred to cTESE, since in most patients with NOA seminiferous tubules containing sperm may be found in the deeper portion of the testicular parenchyma. This may be particularly true for patients with unfavorable histopathological patterns, such as Sertoli cell only syndrome or maturation arrest.
Trial registration number
Not applicable
To assess the role of rare copy number variations in Alzheimer's disease (AD), we conducted a case-control study using whole-exome sequencing data from 522 early-onset cases and 584 controls. The ...most recurrent rearrangement was a 17q21.31 microduplication, overlapping the CRHR1, MAPT, STH and KANSL1 genes that was found in four cases, including one de novo rearrangement, and was absent in controls. The increased MAPT gene dosage led to a 1.6-1.9-fold expression of the MAPT messenger RNA. Clinical signs, neuroimaging and cerebrospinal fluid biomarker profiles were consistent with an AD diagnosis in MAPT duplication carriers. However, amyloid positon emission tomography (PET) imaging, performed in three patients, was negative. Analysis of an additional case with neuropathological examination confirmed that the MAPT duplication causes a complex tauopathy, including prominent neurofibrillary tangle pathology in the medial temporal lobe without amyloid-β deposits. 17q21.31 duplication is the genetic basis of a novel entity marked by prominent tauopathy, leading to early-onset dementia with an AD clinical phenotype. This entity could account for a proportion of probable AD cases with negative amyloid PET imaging recently identified in large clinical series.
Abstract
Study question
Is there any intra-surgical parameter able to predict the outcome of salvage microdissection testicular sperm extraction (mTESE) in patients with previous failed TESE?
Summary ...answer
Among all the variables under consideration, only the seminiferous tubules (ST) caliber pattern found at high magnification was able to significantly predict the mTESE outcome...
What is known already
Several studies have demonstrated that no clinical or hormonal parameters are able to predict the outcome of a salvage mTESE performed in patients with previous sperm retrieval failure (SRF). It has been previously demonstrated that a prediction model with the combination of two intra-surgical parameters such as the STs caliber, defined as dilated tubule (DT), slightly dilated tubules (SDT) and not dilated tubules (NDT), and testis histology had an excellent discrimination ability (AUC 0.93) to distinguish between cases with and without the outcome, but such prediction model has not been tested in patients undergoing salvage mTESE.
Study design, size, duration
A prediction model was built on a dataset of 63 patients, 29–50 years old, undergoing unilateral (15 ) or bilateral (48) salvage mTESE after failed TESE from 2015 through 2019, with a resulting N = 111 testes under consideration. Two models were compared, one with STs and histology as covariates, the other with STs alone: the second model was chosen due to better discrimination...
Participants/materials, setting, methods
we assessed internal validity with a bootstrapping procedure for a realistic estimate of the performance of the prediction model in similar future patients with NOA undergoing salvage mTESE. We repeated the entire modeling process in 259 samples drawn with replacement from the original sample, and determined the performances (AUC, sensitivity, specificity) of the selected prediction model. Calibration (correspondence between the predicted and observed probabilities) was visually assessed by inspecting the calibration belt...
Main results and the role of chance
Sperm retrieval was successful in 24 out of 63 patients (38%): age, testis volume and hormonal parameters did not vary among patients with successful sperm retrieval (SSR) or SRF. The prevalent histological pattern was Sertoli cell only syndrome (69.6%), while hypospermatogenesis, maturation arrest and hyalinosis were found in 4.5%, 23% and 1.8% of cases. The STs pattern was heterogeneous, with DTs being found only in 23.4% of testes. Sperm were found in 69% of DTs, 29% of SDTs, and 5% of NDTs. The prediction model correctly classified 82.88% of patients and explained the 26.5% variability of the outcome. The STs pattern significantly predicted the mTESE outcome with a sensitivity of 62% and a specificity of 90.2%, PPV 69.2%, NPV 87%. Both SDT (OR 0.105, 95% CI 0.034–0.317, p < 0.0001) and NDT (OR 0.024, 95% CI 0.004–0.128, p < 0.0001) were negatively associated with the chance of retrieving sperm, the resulting prediction equation being Log (SSR)= 0.81 – 2.2 SDT – 3.7 NDT. The model had a clearly useful discrimination (AUC 0.813). The optimism corrected AUC was 0.7977, and the model was well calibrated (p = 1.00) with both the 80% and 95% calibration belts encompassing the bisector over the whole range of the predicted probabilities
Limitations, reasons for caution
The STs caliber pattern was subjectively evaluated at high magnification (24–36x) by comparing the individual ST appearance with the surrounding ones, however such evaluation was performed by the same experienced urologist with more than 1000 mTESE procedures performed to date.
Wider implications of the findings: No clinical data but the STs appearance at high magnification could discriminate between patients with and without chances of SSR. These results reinforce the evidence supporting the superiority of mTESE compared to conventional TESE in retrieving sperm, particularly in lower prognosis patients with NOA such as those with previous SR.
Trial registration number
Not applicable
Abstract
Study question
Does the standard, not-dilated seminiferous tubules (STs) diameter vary according with different testis histology patterns in patients with non-obstructive azoospermia (NOA)?
...Summary answer
The standard STs diameter differed significantly among cases with different testis histology: hypospermatogenesis (HYPO) had the highest STs diameter compared to the other histological subgroups.
What is known already
During microdissection testicular sperm extraction (mTESE), the identification of dilated STs, as subjectively evaluated at high magnification by comparing their apparent caliber with that of the surroundings, is crucial to identify residual foci of intact spermatogenesis and to retrieve sperm. Previous studies have demonstrated that dilated STs contain sperm in most cases, but it is not clear why in some cases an apparent normal tubular caliber does not correspond to spermatogenesis integrity. Aim of the present study was to assess whether different histology patterns could affect the STs diameter.
Study design, size, duration
We retrospectively evaluated 168 patients with NOA undergoing unilateral (N = 91) or bilateral (N = 77) mTESE from 2018 through 2019. One or more biopsy samples representative of the overall appearance of the testicular parenchyma were taken from one (for unilateral mTESE) or both testes (for bilateral mTESE), was fixed in Bouin’s solution and sent to the pathologist. Histological analysis was conducted by the same experienced pathologist, who examined at least 100 different tubule sections per biopsy sample.
Participants/materials, setting, methods
Each tubule section (N = 100 per sample) was evaluated at 10X magnification with a micrometer to measure the tubule diameter, then the mean ST diameter was computed. The basal membrane (BM) thickening was evaluated in every section, and a score was assigned by multiplying the degree of BM fibrosis (mild=1, moderate=2, severe=3) for the number of sections (e.g. BM score for moderate fibrosis in 50 sections=2x50=100). Leydig cells hyperplasia (LCH), if present, was also annotated.
Main results and the role of chance
The median + interquartile range STs diameter was 140; 110–185 mm, while the median BM score was 100; 10–150. Sertoli cell only syndrome (SCO) was found in 51.1% of cases, focal SCO (FSCO) in 4,7%, early (EMA) and late (LMA) maturation arrest in 10.2 and 2.73% respectively, HYPO in 26.17% and hyalinosis (HL) in 5% of cases. LCH was found in 46.88% of samples. STs diameter, BM score and LCH differed significantly among the different histological patterns: STs diameter was 125; 100–148 in SCO, 162; 102–187 in FSCO, 130; 100–175 in EMA, 145; 130–195 in LMA, 205; 170–240 in HYPO and 57.5; 42.5–100 in HL. HYPO samples also had the lowest BM score (20;1–100; p < 0.0001) and LCH prevalence (23.8%, p < 0.0001) compared to the other histological subgroups (HS). A multinomial logistic regression for prediction of different histological subgroups was run with STs diameter, BM score and LCH as candidate predictors: the model explained the 29% of variability of the outcome and correctly classified 69% of cases. STs diameter significantly predicted FSCO (RR 1.02, 95% CI 1.0–1.04), LMA (RR 1.02, 95% CI1–1.04) and HYPO (1.03, 95%CI 1.02–1.04), while BM score significantly predicted HL (RR 1.07, 95%CI 1.02–1.13).
Limitations, reasons for caution
The STs were carefully cut before extraction in order to preserve their structural integrity, however the accuracy of such a method of estimating the STs diameter needs to be assessed by further studies.
Wider implications of the findings: The identification of dilated STs remains the best strategy to retrieve sperm by mTESE, since larger STs diameters are mostly associated with the more favorable histological patterns. However, dilated STs may be also found in cases with LMA, which explains why in some cases dilated STs do not contain sper.
Trial registration number
Not applicable
Atlantification of Arctic ocean is causing a sharp increase in temperature and salinity around Svalbard Islands and in Kongsfjorden. Such phenomenon and the input of sediment-rich glacial meltwater ...influence salinity, water column turbidity, and light penetration with ecological implications on the microbial features. With the aim to address the temporal variability of the microbial assemblage in relation to environmental variables, a 7-day study was carried out in Kongsfjorden, in late summer 2013. Abiotic (temperature, salinity, nutrients, total suspended matter, particulate inorganic, and organic carbon) and biotic (phyto -, picophyto-, bacterio-, and virioplankton abundance and microbial respiration) parameters were investigated at a station in the inner fjord area, ca. 8.5 km away from the glacier front. Phyto-, picophyto-, and virioplankton showed low abundance. Dinoflagellates and coccolithophorids dominated the phytoplankton community while
Synechococcus
sp. the picophytoplankton alone, in relation with Atlantic water. Low virus to bacteria ratios were detected, presumably linked to the high sedimentation rates. Interesting variability for picophytoplankton with depth, virioplankton with both time and depth, and respiratory rates with time were found. Moreover, the organic matter turnover was slower on the first sampling day compared to that of the following days. Planktonic abundance depended on the variability of both hydrology (seawater mass inflow) and freshwater runoff from the glacier (relative turbidity degree). Differently, the metabolic rates of respiration appeared to be linked with the particulate carbon pool. Over 1-week study, the diverse microbial dynamics appeared to be conditioned on complex forcing, emphasizing the importance of high-resolution experiment.
The Western areas of the Adriatic Sea are subjected to inputs of inorganic nutrients and organic matter that can modify the trophic status of the waters and consequently, the microbiological ...processes involved in the carbon and phosphorus biogeochemical cycles, particularly in shallow coastal environments. To explore this topic, a survey was carried out during the spring of 2003 in a particular hydrodynamic area of the Gulf of Manfredonia, where the potential (P) and real (R) rates of four different microbial exoenzymatic activities (EEA) (α αG and ß glucosidases ßG, leucine aminopeptidase LAP, and alkaline phosphatase AP) as well as the P and R rates of prokaryotic heterotrophic production (PHP), AP as well as the P and R rates of PHP, primary production (PPnet), the prokaryotic and phototrophic stocks and basic hydrological parameters were examined. Three different water masses were found, with a thermohaline front (THF) being detected between the warmer and less saline coastal waters and colder and saltier offshore Adriatic waters. Under the general oligotrophic conditions of the entire Gulf, a decreasing gradient from the coastal toward the offshore areas was detected, with PHP, PPnet, stocks and EEA (αG, ßG, AP) being directly correlated with the temperature and inversely correlated with the salinity, whereas opposite relationships were observed for LAP activity. No enhancement of microbiological activities or stocks was observed at the THF. The use of P or R rates of microbiological activities, which decrease particularly for EEA, could result in discrepancies in interpreting the efficiency of several metabolic processes.
In the frame of a multidisciplinary international joint effort, supported by CIESM, phytoplankton composition, distribution and activity in summer and late autumn in the Southern Tyrrhenian Sea were ...investigated. The main aim of the study was to obtain a preliminary characterization of the autotrophic community structure of a poorly investigated and complex basin during two contrasting seasonal conditions (stratification vs homogeneity). On both occasions the phytoplankton biomass, as chlorophyll
a, was low in the euphotic layer of water column (8.9
mg
m
−2 in July and 10.7
mg
m
−2 in December), with a clear dominance of the pico-phytoplanktonic component (64% and 76%, respectively), and a pronounced summer Deep Chlorophyll Maximum. Interestingly, primary production was higher in December (429
mg
C
m
−2
d
−1) than July (273
mg
C
m
−2
d
−1), again with a major contribution of pico-class in both seasons (90% and 52% in late autumn and summer, respectively). The dominant contribution of small size classes to the total photosynthetic efficiency and their fast carbon turnover time within the community hint at a preferential carbon pathway through the small-sized components of the food web that contrasts with the traditional views of the Tyrrhenian Sea as a typical component of the temperate Western Mediterranean Sea.
Background
Moderate‐to‐severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and ...their side‐effects. Dupilumab was recently approved for treatment of adolescent AD.
Objectives
A multicentre, prospective, real‐world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate‐to‐severe AD was conducted. The main AD clinical phenotypes were also examined.
Methods
Data of adolescents with moderate‐to‐severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes.
Results
One hundred and thirty‐nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait‐like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS‐CoV‐2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty‐eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event.
Conclusions
Dupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID‐19 pandemic era.
A growing number of neuropsychological studies reported that chemotherapy may impair brain functions, inducing persistent cognitive changes in a subset of cancer survivors. The aim of this paper was ...to investigate the neural basis of the chemotherapy induced neurobehavioral changes by means of metabolic imaging and neuropsychological testing.
We studied the resting brain ¹⁸FFDG-PET/CT images of 50 adult cancer patients with diagnosis of lymphoma: 18 patients were studied prior and 32 after to chemotherapy. All patients underwent to a neuropsychological examination assessing cognitive impairment (tests for shifting attention, verbal memory, phonemic fluency), depression, anxiety and distress.
Compared to no chemotherapy patients, the treated group showed significant bilateral lower rate of glucose metabolism in prefrontal cortices, cerebellum, medial cortices and limbic brain areas. The metabolism of these regions negatively correlated with number of cycles and positively with post-chemotherapy time. The treated group showed a poorer performance in many frontal functions, but similar level of depression, anxiety and distress.
Chemotherapy induced significant long-term changes in metabolism of multiple regions with a prevailing involvement of the prefrontal cortex. The observed cognitive dysfunctions could be explained by these changes. The recovery from chemotherapy is probably affected by treatment duration and by the time elapsed after its end. We speculated that the mechanism could be an accelerating ageing / oxidative stress that, in some patients at risk, could result in an early and persistent cognitive impairment.
