Physiological adaptations of active postmenopausal women and matched men to the multi-day Sardinia Selvaggio Blu wild trek: a gender-comparative pilot study.

PURPOSE: To evaluate the effects of wild trekking by examining, in postmenopausal women, the physiological adaptations to an intensive 5-day wild trek and comparing their responses to those displayed by a group of men of comparable age, training status and mountaineering skills. METHODS: Six healthy, active postmenopausal women in their sixth decade of life participated in the study. Six men of comparable age and training status were also enrolled for gender-based comparisons. The participants traversed the Selvaggio Blu wild trek (Sardinia, Italy) completing a total of 56 km, for an overall height differential of 14,301 m. During all 5-day trek, subjects were supervised by two alpine guides. Changes in body composition, cardiorespiratory fitness, and metabolic patterns of energy expenditure were evaluated before and after the intervention. RESULTS: Total energy expenditure during the trek was significantly higher (p = 0.03) in women (12.88 ± 3.37 kcal/h/kg) than men (9.27 ± 0.89 kcal/h/kg). Extracellular (ECW) and intracellular water (ICW) increased significantly following the trek only in women (ECW: - 3.8%; p = 0.01; ICW: + 3.4%; p = 0.01). The same applied to fat-free mass (+ 5.6%; p = 0.006), fat mass (- 20.4%; p = 0.006), skeletal muscle mass (+ 9.5%; p = 0.007), and appendicular muscle mass (+ 7.3%; p = 0.002). Peak VO2/kg (+ 9.4%; p = 0.05) and fat oxidation (at 80 W: + 26.96%; p = 0.04; at 100 W: + 40.95%; p = 0.02; at 120 W: + 83.02%; p = 0.01) were found increased only in women, although no concurrent changes in partial pressure of end-tidal CO2 (PETCO2) was observed. CONCLUSIONS: In postmenopausal women, a 5-day, intensive and physically/technically demanding outdoor trekking activity led to significant and potentially relevant changes in body composition, energy balance and metabolism that are generally attained following quite longer periods of training.

Risk factors associated with low back pain in competitive female gymnasts: A meta-analytic approach.

The aim of this meta-analysis was to aggregate data from studies investigating the risk factors associated with low back pain (LBP) in competitive gymnasts.Four databases were searched and studies reporting demographics, anthropometrics, functional, psychosocial and gymnastics-practice variables in competitive gymnasts with and without LBP were included. For continuous data, the weighted mean difference (MD) and confidence interval (95% CI) were calculated, while odds or risk ratio (OR, RR) were calculated for dichotomous data.Meta-analysis of six cross-sectional studies involving 284 competitive female gymnasts revealed that artistic were more likely to report LBP compared to rhythmic gymnasts (RR 1.4, 95% CI 1.04-2.0, Z=2.2, p=0.03). Data pooling revealed that age (MD 1.5 years, 95% CI 0.4-2.5, p=0.005) and body weight (MD 3.5 kg, 95% CI 0.1-6.8, p=0.04) were significantly higher in gymnasts with LBP compared to those without. Subgroup-analyses confirmed these differences in artistic but not in rhythmic gymnasts. Moreover, artistic gymnasts with LBP tended to display longer gymnastics-practice history (p=0.09) compared to those without.Increased age, body weight and, to a lesser extent, longer gymnastics-practice appear to differentiate artistic gymnasts with LBP from those without; conversely, these potential risk factors seem less relevant for rhythmic gymnasts.

Posterior tibial perforators relationship with superficial nerves and veins: A cadaver study.

BACKGROUND: Most authors have evaluated the location of lower leg arterial perforators, but little is still known about the relationship between the arterial network and great saphenous vein (GSV) and saphenous nerve (SN). The aim of this study is to evaluate the relationship between the arterial network of the posterior tibial artery perforators, the cutaneous nerves, and the superficial venous system in the lower one third of the leg. METHODS: Eighteen lower limbs from cadavers were used for this study. The arterial and venous compartment were selectively injected with a mixture of barium sulfate and epoxy. The specimen were CT scanned and the superficial veins, nerves, and the arterial perforators were dissected. RESULTS: A large perforator of the posterior tibial artery was found at a mean distance of 6.23 cm ± 0.88, with a 95% CI: 5.79-6.67, from the medial malleolus. The average diameter was 0.9 mm ± 0.17, with a 95% CI: 0.81-0.99. In 67% the connection of the venae comitantes to the superficial venous system was established with the GSV, in the other cases, with Leonardo's vein. Both dissection and imaging studies showed perineural interperforator connections along the branches of SN in all the specimens examined. CONCLUSIONS: The distribution pattern of posterior tibial artery perforators followed the superficial nerves in this region. There is an interperforator anastomotic network along the SN. The various patterns of the venous drainage system, in relationship to the distribution of the branches of posterior tibial artery perforators, have been clarified.

Correction: Bellu et al. Smart Nanofibers with Natural Extracts Prevent Senescence Patterning in a Dynamic Cell Culture Model of Human Skin. Cells 2020, 9, 2530.

In the original publication [...].

Partial trisomy of the long arm of chromosome 1: prenatal diagnosis, clinical evaluation and cytogenetic findings. Case report and review of the literature.

Partial trisomy of the long arm of chromosome 1 is a relatively rare cytogenetic anomaly. Its phenotype has still not been completely defined, because of the cytogenetic heterogeneity of the cases so far described. We report a prenatal case of partial 1q trisomy associated with partial monosomy 4q, secondary to balanced maternal translocation t(1;4). The trisomic segment extended from 1q31.1 to qter and the monosomy 4q was from 4q35.2 to qter. The phenotypic anomalies found by post-mortem and autopsy examinations were compared with those of similar cases reported in the literature. We performed standard cytogenetics and fluorescence in situ hybridization. Cerebral ventriculomegaly, present in our case, seemed to be a constant feature in partial 1q trisomies, so this cerebral malformation could be considered as the main echographic marker for this chromosomal imbalance and trisomy 1q should be added to the list of chromosomal abnormalities associated with ventriculomegaly.

Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

Low back pain prevalence and risk factors in Italian adolescent male soccer players: results from an online survey.

BACKGROUND: The purpose of this retrospective survey was to analyze the prevalence of low back pain (LBP) among Italian adolescent soccer players, and to identify potential risk factors. METHODS: Participants were requested to answer an online survey based on the standardized Nordic questionnaires for musculoskeletal symptoms. RESULTS: Data were obtained from 204 male soccer players aged 14-17 years competing at the national and regional level. More than half of the players had experienced LBP in their lives. One-way ANOVA revealed that the players with LBP were taller, heavier and with a higher BMI (all P values<0.00001). When considering the playing position, ANOVA revealed that 14-15 years-old strikers displayed higher LBP scores than all other roles (all P values<0.05). Accordingly, strikers were exposed to a higher risk of LBP than midfielders (RR=1.48; 95% CI: 1.10-2.01; P=0.01) and goalkeepers (RR=1.48; 95% CI: 1.02-2.971; P=0.04), but not defenders (RR=1.23; 95% CI: 0.93-1.63; P=0.15). Within the 14-15 age-class, strikers were, again, those most exposed to LBP risk (all P values<0.05). CONCLUSIONS: Anthropometric and soccer-related features should be monitored to ensure early identification of potential risk factors for LBP. This information should be considered along with the specific playing position as strikers emerged as the roles most exposed to LBP risk.

Development of polymeric microbubbles targeted to prostate-specific membrane antigen as prototype of novel ultrasound contrast agents.

Ultrasound-targeted microbubbles (MBs) offer new opportunities to enhance the capabilities of diagnostic ultrasound (US) imaging to specific pathological tissue. Herein, we report on the design and development of a novel prototype of US contrast agent based on polymeric MBs targeted to prostate-specific membrane antigen (PSMA) for use in the diagnosis of prostate cancer (PCa). First, a set of air-filled MBs by a variety of biocompatible polymers were prepared and characterized in terms of morphology and echogenic properties after exposure to US. MBs derived from poly(D,L-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG) copolymer resulted as the most effective in terms of reflectivity. Such polymer was therefore preconjugated with a urea-based PSMA inhibitor molecular probe (DCL), and the obtained MBs were investigated in vitro for their targeting efficacy toward PSMA positive PCa (LNCaP) cells. Fluorescence microscopy proved a specific and efficient adhesion of targeted MBs to LNCaP cells. To our knowledge, this work reports the first model of polymeric MBs appropriately engineered to target PSMA, which might be further optimized and used for PCa diagnosis and potential carriers for selective drug delivery.

Natural Compounds and PCL Nanofibers: A Novel Tool to Counteract Stem Cell Senescence.

Tissue homeostasis mainly depends on the activity of stem cells to replace damaged elements and restore tissue functions. Within this context, mesenchymal stem cells and fibroblasts are essential for maintaining tissue homeostasis in skin, in particular in the dermis. Modifications in collagen fibers are able to affect stem cell features. Skin properties can be significantly reduced after injuries or with aging, and stem cell niches, mainly comprising extracellular matrix (ECM), may be compromised. To this end, specific molecules can be administrated to prevent the aging process induced by UV exposure in the attempt to maintain a youngness phenotype. NanoPCL-M is a novel nanodevice able to control delivery of Mediterranean plant myrtle (Myrtus communis L.) extracts. In particular, we previously described that myrtle extracts, rich in bioactive molecules and nutraceuticals, were able to counteract senescence in adipose derived stem cells. In this study, we analyzed the effect of NanoPCL-M on skin stem cells (SSCs) and dermal fibroblasts in a dynamic cell culture model in order to prevent the effects of UV-induced senescence on proliferation and collagen depot. The BrdU assay results highlight the significantly positive effect of NanoPCL-M on the proliferation of both fibroblasts and SSCs. Our results demonstrate that-M is able to preserve SSCs features and collagen depot after UV-induced senescence, suggesting their capability to retain a young phenotype.

Neuroanatomy, the Achille's Heel of Medical Students. A Systematic Analysis of Educational Strategies for the Teaching of Neuroanatomy.

Neuroanatomy has been deemed crucial for clinical neurosciences. It has been one of the most challenging parts of the anatomical curriculum and is one of the causes of "neurophobia," whose main implication is a negative influence on the choice of neurology in the near future. In the last decades, several educational strategies have been identified to improve the skills of students and to promote a deep learning. The aim of this study was to systematically review the literature to identify the most effective method/s to teach human neuroanatomy. The search was restricted to publications written in English language and to articles describing teaching tools in undergraduate medical courses from January 2006 through December 2017. The primary outcome was the observation of improvement of anatomical knowledge in undergraduate medical students. Secondary outcomes were the amelioration of long-term retention knowledge and the grade of satisfaction of students. Among 18 selected studies, 44.4% have used three-dimensional (3D) teaching tools, 16.6% near peer teaching tool, 5.55% flipped classroom tool, 5.55% applied neuroanatomy elective course, 5.55% equivalence-based instruction-rote learning, 5.55% mobile augmented reality, 5.55% inquiry-based clinical case, 5.55% cadaver dissection, and 5.55% Twitter. The high in-between study heterogeneity was the main issue to identify the most helpful teaching tool to improve neuroanatomical knowledge among medical students. Data from this study suggest that a combination of multiple pedagogical resources seems to be the more advantageous for teaching neuroanatomy.

A human MMTV-like betaretrovirus linked to breast cancer has been present in humans at least since the copper age.

The betaretrovirus Mouse Mammary Tumor Virus (MMTV) is the well characterized etiological agent of mammary tumors in mice. In contrast, the etiology of sporadic human breast cancer (BC) is unknown, but accumulating data indicate a possible viral origin also for these malignancies. The presence of MMTVenv-like sequences (MMTVels) in the human salivary glands and saliva supports the latter as possible route of inter-human dissemination. In the absence of the demonstration of a mouse-man transmission of MMTV, we considered the possibility that a cross-species transmission could have occurred in ancient times. Therefore, we investigated MMTVels in the ancient dental calculus, which originates from saliva and is an excellent material for paleovirology. The calculus was collected from 36 ancient human skulls, excluding any possible mouse contamination. MMTV-like sequences were identified in the calculus of 6 individuals dated from the Copper Age to the 17th century. The MMTV-like sequences were compared with known human endogenous betaretroviruses and with animal exogenous betaretroviruses, confirming their exogenous origin and relation to MMTV. These data reveal that a human exogenous betaretrovirus similar to MMTV has existed at least since 4,500 years ago and indirectly support the hypothesis that it could play a role in human breast cancer.

Smart Nanofibers with Natural Extracts Prevent Senescence Patterning in a Dynamic Cell Culture Model of Human Skin.

Natural cosmetic products have recently re-emerged as a novel tool able to counteract skin aging and skin related damages. In addition, recently achieved progress in nanomedicine opens a novel approach yielding from combination of modern nanotechnology with traditional treatment for innovative pharmacotherapeutics. In the present study, we investigated the antiaging effect of a pretreatment with Myrtus communis natural extract combined with a polycaprolactone nanofibrous scaffold (NanoPCL-M) on skin cell populations exposed to UV. We set up a novel model of skin on a bioreactor mimicking a crosstalk between keratinocytes, stem cells and fibroblasts, as in skin. Beta-galactosidase assay, indicating the amount of senescent cells, and viability assay, revealed that fibroblasts and stem cells pretreated with NanoPCL-M and then exposed to UV are superimposable to control cells, untreated and unexposed to UV damage. On the other hand, cells only exposed to UV stress, without NanoPCL-M pretreatment, exhibited a significantly higher yield of senescent elements. Keratinocyte-based 3D structures appeared disjointed after UV-stress, as compared to NanoPCL-M pretreated samples. Gene expression analysis performed on different senescence associated genes, revealed the activation of a molecular program of rejuvenation in stem cells pretreated with NanoPCL-M and then exposed to UV. Altogether, our results highlight a future translational application of NanoPCL-M to prevent skin aging.

Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia.

The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia's genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period. The earliest individuals show a strong affinity to western Mediterranean Neolithic populations, followed by an extended period of genetic continuity on the island through the Nuragic period (second millennium BCE). Beginning with individuals from Phoenician/Punic sites (first millennium BCE), we observe spatially-varying signals of admixture with sources principally from the eastern and northern Mediterranean. Overall, our analysis sheds light on the genetic history of Sardinia, revealing how relationships to mainland populations shifted over time.

Agenesis of the posterior arch of the atlas and complex alterations of the craniovertebral junction: A case report.

The craniovertebral junction is a unique part of the somite-derived axial skeleton. The absence or hypoplasia of the posterior arch of C1 is frequently associated with compensatory hypertrophy of the anterior arch of C1 and of the spinous process of C2. Here, we report a patient with agenesis of the posterior arch of C1 without neurologic deficits. Our patient presented with complex alterations of the craniovertebral junction that involved interactions between the condyles, clivus, atlas, and epistropheus. To our knowledge, dislocation of the odontoid process above the Chamberlain line, including cranial migration of the anterior arch of C1, has not been reported in the literature.

Association of Klippel-Feil syndrome, Dandy-Walker malformation, spina bifida: A case report.

Klippel-Feil syndrome is a congenital malformation characterized by the fusion of at least 2 cervical vertebrae. It may occur in association with other clinical syndromes and disorders. We describe a case of prenatal diagnosis of a Klippel-Feil syndrome with Dandy-Walker malformation, and spina bifida, proved by ultrasound examination. A postmortem x-ray and autopsy were performed in a female fetus of 16 + 6 weeks of gestation: several malformations have been discovered. To the best of our knowledge, no similar cases have been reported in the medical literature. This case report underscores the importance of a careful ultrasound screening during pregnancy for an adequate diagnostic and therapeutic management.

Real-time telemetry monitoring of oxygen in the central complex of freely-walking Gromphadorhina portentosa.

A new telemetric system for the electrochemical monitoring of dissolved oxygen is showed. The device, connected with two amperometric sensors, has been successfully applied to the wireless detection of the extracellular oxygen in the central complex of freely-walking Gromphadorhina portentosa. The unit was composed of a potentiostat, a two-channel sensor conditioning circuit, a microprocessor module, and a wireless serial transceiver. The amperometric signals were digitalized and sent to a notebook using a 2.4 GHz transceiver while a serial-to-USB converter was connected to a second transceiver for completing the communication bridge. The software, running on the laptop, allowed to save and graph the oxygen signals. The electronics showed excellent stability and the acquired data was linear in a range comprised between 0 and -165 nA, covering the entire range of oxygen concentrations. A series of experiments were performed to explore the dynamics of dissolved oxygen by exposing the animals to different gases (nitrogen, oxygen and carbon dioxide), to low temperature and anesthetic agents (chloroform and triethylamine). The resulting data are in agreement with previous O2 changes recorded in the brain of awake rats and mice. The proposed system, based on simple and inexpensive components, can constitute a new experimental model for the exploration of central complex neurochemistry and it can also work with oxidizing sensors and amperometric biosensors.

Patau syndrome with long survival in a case of unusual mosaic trisomy 13.

We report a 12-year-old patient with Patau syndrome, in whom two cell lines were present from birth, one with total trisomy 13 due to isochromosome (13q), and one with partial trisomy 13. A cytogenetic re-evaluation at 9 years of age brought to light in skin fibroblasts a third cell line, partially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were characterized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the results suggested a sequence of rearrangements which beginning from an isochromosome (13q) could have led to the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentary lesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on different tissues, including skin fibroblasts from differently pigmented areas, are also reported.

Metals in bones of the middle-aged inhabitants of Sardinia island (Italy) to assess nutrition and environmental exposure.

Metals in bones of 72 subjects lived between the twelfth and eighteenth century AC and collected in four Sardinian (Italian insular region) burial sites (Alghero, Bisarcio, Geridu, and Sassari) were determined and used as biomarkers to evaluate diet and potential social-environmental differences. Concentrations of Ba, Ca, Cd, Cu, Hg, Pb, Sr, and Zn were quantified in different types of compact bone (femur, fibula, humerus, radius, tibia, ulna) by sector field inductively coupled plasma mass spectrometry previous acidic digestion and differences among the various burial sites, centuries, types of bone, gender, and age were explored by univariate and multivariate analyses. Results indicated differences between sites in terms of diet: Bisarcio (inland village) had increased ratios of Ba/Ca and Zn/Ca due to higher incidence of vegetables, cereals, and animal foods in the diet; Geridu (coastal village) showed increased Sr/Ca ratio indicating foods of plant and marine origin that were predominant; Alghero (coastal site) and Sassari (inland site) displayed prevalently a mixed diet reflecting a higher economy and food imports. In addition, these latter sites showed increased levels of Hg/Ca (fish, drugs, cosmetics) and Pb/Ca (coins, utensils, pipeline for water). In conclusion, the elemental Ba/Ca, Sr/Ca, and Zn/Ca ratios were indicative of provenance and diet, while Hg/Ca and Pb/Ca ratios were associated to various forms of environmental exposure.

Pure partial trisomy of 6p12.1-p22.1 secondary to a familial 12/6 insertion in two malformed babies.

We describe two malformed infants with trisomy 6p12.1-p22.1 due to 12/6 interchromosomal insertion. The phenotypic data observed in these patients are compared chiefly with a case cytogenetically similar described by Villa et al. [A. Villa, E.G. Gomez, L. Rodriguez, R.H. Rastrollo, M.E. Martinez Tallo, M.L. Martinez-Frias, Interstitial tandem duplication of 6p: a case with partial trisomy (6)(p12p21.3), Am. J. Med. Genet. 90 (2000) 369-375]. All three infants are trisomic for a genomic segment which largely overlaps that reported as duplicated in previous cases, but with the addition of a more proximal segment, extending from 6p12 to 6p21. We suggest that some of their phenotypic anomalies are due to the trisomy of this chromosomal region. We also speculate on the possible role played by the TFAP2B (Transcription Factor AP2-beta) gene, which is one of the genes mapped on the duplicated segment.

Posterior Arch Defect of the Atlas Associated to Absence of Costal Element of Foramen Transversarium from 16th-Century Sardinia (Italy).

STUDY DESIGN: A paleopathological case of posterior arch defect of the atlas associated to the absence of costal element of the foramen transversarium. OBJECTIVE: In living patients as well as in postmortem analysis it should be difficult to distinguish between a congenital and an acquired anomaly. Any anomaly in the anatomy of atlas should be taken into consideration by clinicians, surgeons, radiologists, and anatomists in order to avoid misinterpretations and clinical complications. SUMMARY OF BACKGROUND DATA: Posterior arch defect has a current occurrence of approximately 4%. Posterior arch schisis is attributed to the defective or absent development of the cartilaginous preformation of the arch rather than a disturbance of the ossification. The absence of costal element of the foramen transversarium has an incidence of ranging from 2% to 10% and is attributed to a developmental defect or to variations in the course of the vertebral artery. METHODS: The skeleton of a man aged 20-30 years, brought to light in the plague cemetery of 16th century Alghero (Sardinia), showed anomalies of the atlas, consisting in failure of the midline fusion of the 2 hemiarches with a small gap and an open anterior foramen trasversarium on the left side. A macroscopic, radiological, and stereomicroscopic study was carried out. RESULTS: The study allowed to rule out a traumatic origin of the defects and to diagnose an association of 2 congenital anomalies. CONCLUSION: Osteoarchaeological cases provides with a valuable opportunity to examine and describe variations in the anatomy of the atlas. LEVEL OF EVIDENCE: N/A.