Is the phosphoinositol 1,3-kinase/protein kinase B (PI3K/AKT) pathway expression profile in cumulus cells (CCs) a potential marker of oocyte competence and predictive of pregnancy outcome?
Eleven ...genes (AKT1, ARHGEF7, BCL2L1, CCND1, E2F1, HRAS, KCNH2, PIK3C2A, SHC1, SOS1 and SPP1) in the PI3K/AKT pathway were significantly down-regulated in CCs from oocytes that went on to produce a pregnancy compared to CCs associated with a negative outcome.
The PI3K/AKT pathway plays a pivotal role in the interdependence and continuous feedback between the oocyte and CCs.
The expression analysis of 92 transcripts in the PI3K/AKT pathway in CCs from patients with negative or positive pregnancy outcome, after single embryo transfer, was performed. Mouse CCs target gene expression was conducted to associate the expression profile of PI3K/AKT pathway to oocyte developmental profile.
Fifty-five good prognosis IVF patients who had been referred to IVF or intracytoplasmic sperm injection treatment for male-factor infertility or tubal disease were enroled. CCs from single cumulus-oocyte complexes (COCs) from 16 patients who underwent a single embryo transfer were analyzed. Twenty-five CD-1 mice were used to assess gene expression in CCs associated with oocytes with different competence in relation to hCG priming. A total 220 human COCs were collected. The RNA extracted from CCs of 16 selected patients was used to analyze PI3K/AKT pathway gene expression employing a 96-well custom TaqMan Array. Expression data of CCs associated to positive IVF outcome were compared to data from negative outcome samples. Mice were sacrificed after 9, 12, 15, 21 and 24 h post-hCG administration to obtain CCs from MII oocytes with different developmental competence. Akt1, Bcl2l2 and Shc1 expression were tested in the collected mouse CCs. In addition, the expression of upstream regulator ESR1, the gene encoding for the oestrogen receptor ERβ, and the downstream effectors of the pathway FOXO1, FOXO3 and FOXO4 was evaluated in human and mouse samples.
Transcripts involved in the PI3K Signaling Pathway were selectively modulated according to the IVF/ICSI outcome of the oocyte. Eleven transcripts in this pathway were significantly down-regulated in all samples of CCs from oocytes with positive when compared those with a negative outcome. These outcomes were confirmed in mouse CCs associated with oocytes at different maturation stages. Expression data revealed that the down-regulation of ESR1 could be related to oocyte competence and is likely to be the driver of expression changes highlighted in the PI3K/AKT pathway.
Small sample size and retrospective design.
The CCs expression profile of PI3K/AKT signaling genes, disclosed a specific CCs gene signature related to oocyte competence. It could be speculated that CCs associated with competent oocytes have completed their role in sustaining oocyte development and are influencing their fate in response to metabolic and hormonal changes by de-activating anti-apoptotic signals.
Supported by Merck Serono an affiliate of Merck KGaA, Darmstadt, Germany (research grant for the laboratory session; Merck KGaA reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors). The authors declare no conflict of interest.
We performed a pilot study with the purpose to evaluate the prevalence of sarcopenia in osteoporotic women with vertebral fractures. Dual-energy X-ray absorptiometry (DXA) was used to measure the ...whole and regional body composition. Appendicular lean mass (aLM) was calculated as the sum of lean mass in arms and legs. We calculated the skeletal muscle mass index (aLM/h
2
), and we measured bone mineral density and
T
scores by DXA scan at total-body and at femoral neck. Participants were divided according to the number of vertebral fractures (single or multiple fractures). A total of 67 women were included. Thirty-five women (52.23 %) had a vertebral fracture, of them 8 (22.85 %) were sarcopenic and 32 women (47.76 %) had multiple vertebral fractures, of them 14 (43.75 %) were sarcopenic. Our results suggest that sarcopenia is common among osteoporotic women increasing along with the number of vertebral fragility fractures.
Background
Free vascularized fibula flap represents the gold standard vascularized bone graft for the management of segmental long bone defects after traumatic injury. The current study represents ...the largest retrospective multicenter data collection on the use of free fibula flap (FFF) for extremities' orthoplastic reconstruction after trauma aiming to highlight current surgical practice and to set the basis for updating current surgical indications.
Methods
The study is designed as a retrospective analysis of prospectively collected data between 2009 and 2021 from six European University hospitals. Patients who underwent fibula flap reconstruction after acute traumatic injury (AF) or as a late reconstruction (LF) after post‐traumatic non‐union of upper or lower limb were included. Only extra‐articular, diaphyseal fracture were included in the study. Surgical data were collected. Time to bone healing and complications were reported as clinical outcomes.
Results
Sixty‐two patients were included in the study (27 in the AF group and 35 in the LF group). The average patients' age at the time of the traumatic event was 45.3 ± 2.9 years in the AF group and 41.1 ± 2.1 years in the LF group. Mean bone defect size was 7.7 ± 0.6 cm for upper limb and 11.2 ± 1.1 cm (p = .32) for lower limb. Bone healing was uneventful in 69% of treated patients, reaching 92% after complementary procedures. Bone healing time was 7.6 ± 1.2 months in the acute group and 9.6 ± 1.5 months in the late group. An overall complication rate of 30.6% was observed, with a higher percentage of late bone complications in the LF group (34%), mostly non‐union cases.
Conclusions
FFF reconstruction represents a reliable and definitive solution for long bone defects with bone healing reached in 92% cases with a 8.4 months of average bone healing time.
This work aims to assess lower limb free flaps spontaneous sensory recovery by comparing and analyzing a single standardized reconstructive procedure, namely the free noninnervated anterolateral ...thigh (ALT) flap in order to evaluate which flap or patient-related factors may predict flap reinnervation.
Between January 2010 and March 2018 all nonreinnervated ALT flaps for lower limb coverage performed at our institution were screened. We excluded from the study flaps with less than 18 months of follow-up time, neurotized flaps, and those from patients who missed the last follow up. Sensory modalities that were evaluated included the two-point discrimination (2PD) test, measured in mm; and the Semmes-Weinstein monofilament (SWM) test, measured in gram. The sensory parameter results were compared and analyzed according to flap size (two groups; <160 cm
2
vs. > 160 cm
2
), and post-op time of testing (two groups; <18-28 months vs. > 28 months).
Twenty-one ALT free flaps were finally retained by this study. Our findings showed that flaps of smaller surface area showed a significantly better return in sensory discrimination 2PD and in sensory cutaneous pressure perception SWM testing.
This work establishes for the first time some key quantitative data that can help predict free flap spontaneous reinnervation outcomes when using the same ALT flap. In our series, flaps surface remains the main discriminant value for a better sensory recovery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Retromolar trigone (RMT) cancer is a rare malignancy, which develops in a narrow area of the oral cavity. Surgical intervention requires wide excision and appropriate reconstruction usually with a ...free tissue transfer. Little has been published regarding the ideal microvascular reconstruction, mainly focusing on radial forearm and anterolateral thigh free flap. The medial sural artery perforator flap (MSAP) is not new for head and neck reconstruction but its use for RMT reconstruction has not been previously explored. The purpose of the study is to present a multicentric case series investigating the reliability of MSAP flap for RMT reconstruction.
The study is designed as a retrospective case series. All patients diagnosed with RMT cancer and undergone surgical resection and immediate reconstruction with a MSAP flap between February 2016 and March 2020 were identified. Patients' demographics and surgical details were collected. Functional results were evaluated using the Head and Neck Module of the European Organization for Research and Treatment of Cancer at 12 months of follow-up. A total of 34 patients with a mean age of 58 years were included in the study. An average defect size of 31.5 cm
was observed after RMT tumor resection.
The MSAP flaps' average dimensions were 11 ± 3.1 cm in length and 4.7 ± 1.6 cm in width with a mean thickness of 1.4 ± 0.8 cm. No flap complications were observed in 28 cases; four patients developed an orocutaneous fistula. One patient needed surgical revision for venous congestion while only one case of flap failure was observed. At 12 months of follow-up, 87% of the patient cohort had normal, understandable speech. No patient experienced complete loss of swallowing. Results of the H&N35 module showed a significative postoperative improvement in mouth soreness, mouth opening and social (p < .05*). No patient complained difficulty in motility at the donor site.
The MSAP flap appears to be appropriate for RMT reconstruction and could be considered the workhorse for small to medium size defect of RTM region. It has a long pedicle of matching caliber and provides adequate tissue volume with minimal donor site morbidity.
Bone marrow macrophages of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies of undetermined significance (MGUS) and benign anemia (controls) were stimulated for 7 ...days with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and analysed for the expression of endothelial cell (EC) markers by reverse transcription (RT)-PCR, real-time RT-PCR, western blot and immunofluorescence. Their vasculogenic ability was investigated in vitro in a Matrigel assay and in vivo on bone marrow biopsies through dual immunofluorescence and confocal laser microscopy. Active MM macrophages exposed to VEGF and bFGF acquired EC markers and formed capillary-like structures mimicking paired bone marrow ECs (multiple myeloma patient-derived endothelial cells, MMECs), with major responsiveness compared to macrophages from nonactive MM, MGUS or controls. Bone marrow biopsies of active MM harbored 'mosaic' vessels, being formed by MMECs, EC-like macrophages and macrophages themselves. These figures were rare in nonactive MM and absent in MGUS or controls. Our data indicate that macrophages contribute to build neovessels in active MM through vasculogenic mimicry, and this ability proceeds parallel to progression of the plasma cell tumors. Macrophages may be a target for the MM antivascular treatment.
Simulation in microsurgery is an important pillar of training and maintenance of surgical skills. Between learning microsurgical skills and mastering them in clinical practice, the usefulness of ...low-fidelity simulators for improving microsurgery skills has been well documented. Nowadays the in vivo models represent the gold standard of microsurgical training; however, their use implies difficulties and limitations. We developed a portable, low-cost, and modern device to help trainees to practice at their convenience to maintain their microsurgical suturing skills. By using CAD and 3D printer designs, we developed a “microsurgery trainer” that contains a middle section with eight projections with holes, arranged as a circle. The idea is to pass the microsuture—preferably 7/0 or 8/0 sutures—in a clockwise manner—with the needle passing from “out to in” and “in to out” through each hole. This allows the trainee to use his/her wrist to be flexible and achieve better control over the micro needle. Studies evaluating the potential of such a device in shortening the learning curve are needed and will be crucial to define whether the “microsurgery arena” will help trainees to obtain better outcomes in microsurgical practice.
This paper focuses on education and skills mismatch among Italian graduates. Indicators for over- and under-utilization of education and under-utilization of skills are included as explanatory ...factors in a wage equation, testing theories that could explain the effect of over-schooling on wages. We find little evidence to support assignment theory and also identify a relatively weak wage effect arising from educational mismatch associated with employers', as opposed to employees', perceptions of the job requirements. Our interpretation is that some employers have re-categorized jobs as requiring a degree, when they were previously filled by non-graduates, and many have not altered pay scales accordingly.
Restoring function after traumatic defects of the palm is a reconstructive challenge, considering the need for flexible, elastic, and resistant skin. Dermal skin substitutes are biologically ...engineered materials composed of collagen and glycosaminoglycan, devoid of cellular structures. These biodegradable materials act as artificial dermis and stimulate neovascularizationthey have been used for many years, mainly on the dorsal side of the hand and fingers, whereas the palmar side of the hand has been generally addressed by local flaps. In this study, we described our experience with dermal skin substitutes in two cases of palmar defects associated with exposed tendinous structures. Coverage of palmar defects in hand and fingers with dermal substitute and split thickness skin graft was performed on two patients. Both patients presented palmar-only loss of tissue (traumatic palmar amputation in the first patient and degloving-type injury in the second patient). Range of motion, functional outcomes, and satisfaction and aesthetical results were evaluated. The resulting skin showed good quality, thickness, pliability, and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Additionally, the patients regained full range of motion and reported high satisfaction. The association of split thickness skin graft with dermal substitutes in palmar traumatic hand showed optimal functional and aesthetic outcomes. Although being more adapted to dorsal loss of substance, collagen-based dermal substitutes can also be useful reconstructive tools in palmar defects with exposed structures and could be used to a larger extent in the future.
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