Reducing the time of sperm-oocyte interaction in human in-vitro fertilization improves the implantation rate

Human oocyte development was evaluated after a reduced timeexposure to spermatozoa in vitro. A total of 119 patients wereassigned to two study groups in a randomized prospective studyin which each patient‘s oocytes were exposed to spermatozoafor either 1 h (group 1 – 58 patients) or the standard16 h incubation period (group 2 – 61 patients). The fertilizationrate obtained in group 1 was higher than in group 2 (285/393,73%, and 272/410, 66% respectively), suggesting that the spermatozoa-oocyteinteraction occurs within 1 h. This was confirmed in a studyin vitro using fluorescently labelled spermatozoa and normaloocyte-cumulus complexes. Spermatozoa enter the cumulus complexwithin 15 min, traverse the cumulus layer within 3 h, and firstappear in the oocyte cortex at 4 h post-insemination. The incidenceof polyspermy was higher in oocytes exposed to spermatozoa for16 h (3%) than for 1 h (1%). There was no difference in thecleavage rate or morphological characteristics of embryos fromboth study groups. However, when evaluating the timing of embryodevelopment, group 1 generated a significantly higher percentageof four to five cell embryos when compared to group 2 (55 versus39%; P < 0.001), documented at 40 h post-insemination. Theimplantation and pregnancy rates for group 1 were 11 and 28%,while the corresponding rates for group 2 were 8 and 15%. Thissuggests that a reduced exposure of oocyte to spermatozoa favoursembryo viability, possibly due to a decrease in potential damagefrom sperm metabolic waste products.     

Cell proliferation in breast cancer is a major determinant of clinical outcome in node-positive but not in node-negative patients.

The growth rate of a tumor cell population depends on two major factors: the percentage of proliferating cells (cell growth fraction) and the rapidity of their duplication (cell proliferation rate). The authors evaluated the prognostic and predictive value of both kinetics parameters in a large series of breast cancer patients (n=504). The cell growth fraction was determined by MIB-1 immunostaining, the cell proliferation rate by AgNOR analysis. Ki-67 LI (labeling index) and AgNOR area were significantly associated with histotype, histologic grade, tumor size, estrogen/progesterone receptor status, patient age, and lymph node involvement (P<0.005). In the entire series of patients, both kinetics variables were significantly and independently associated with the clinical outcome, but their prognostic relevance was quite different when node-negative and node-positive patients were considered separately. Although in node-positive patients Ki-67 LI and AgNOR area were the unique independent predictors of disease-free and overall survival, they were excluded by the multivariate Cox model in node-negative patients, where only tumor size and estrogen receptor status retained a significant P-value. These results show that in breast carcinoma the cell growth fraction and the cell proliferation rate have a different prognostic impact with respect to the lymph node status and are major determinants of clinical outcome in node-positive patients only. Within this subgroup, the rapidity of cell proliferation as assessed by AgNOR analysis also served as a sensitive predictor of the response to adjuvant treatments.     

Psoriasis arthropathica. A review of the literature, general considerations and the authors' personal experience]

A retrospective study has been carried out on 897 psoriatic patients in order to verify the incidence and radiological patterns of psoriatic arthropathy (PA). Site of involved joints, appearance and degree of involvement were correlated with extent of skin disease and blood test results. Sixty-five patients (7%) showed "clinical" arthritis whereas only 20 cases (2.2%) were radiologically positive; among them, 35% were classified as "severe" forms. Peripheral arthritis was observed in all cases, involving the hand in 85% of patients. The distal interphalangeal joints were the most affected location in the feet (78%) and the proximal interphalangeal joints in the hands (94%). The extant small peripheral joints were involved in decreasing rates proceeding proximally. Bilateral and asymmetric involvement was observed in most of the patients; hypertrophic interphalangeal joints erosion was the typical pattern in 100% of cases, evolving in rheumatoid-like ankylosis in 23% of them. Spondylitis and/or sacroiliitis were associated in 50% of patients. No correlation between degree of arthritis and skin disease was found in our series, with the exception of proximal and axial joints arthritis, in which extensive skin disease and severe small joints involvement were associated in 80% of cases. Clear differential features were demonstrated between peripheral PA and rheumatoid arthritis, and between spinal involvement in PA and ankylosing spondylitis. Poor correlation of distal arthritis to psoriatic nail involvement was also demonstrated.     

Microneedling for the treatment of hair loss?

Microneedling is a minimally invasive dermatological procedure in which fine needles are rolled over the skin to puncture the stratum corneum. This therapy is used to induce collagen formation, neovascularization and growth factor production of treated areas. It has been used in a wide range of dermatologic conditions, including androgenetic alopecia (AGA) and alopecia areata, among others. While there are a limited number of studies examining this therapy in the use of hair loss, microneedling has been successfully paired with other hair growth promoting therapies, such as minoxidil, platelet‐rich plasma and topical steroids, and shown to stimulate hair follicle growth. It is thought that microneedling facilitates penetration of such first‐line medications, and this is one mechanism by which it promotes hair growth. To date, the area most studied and with the most success has been microneedling treatment of AGA. While the current evidence does not allow one to conclude superiority of microneedling over existing standard therapies for hair loss, microneedling shows some promise in improving hair growth, especially in combination with existing techniques. This review summarizes the current literature regarding microneedling in the treatment of alopecia and calls for further studies to define a standard treatment protocol.     

Consensus on melanonychia nail plate dermoscopy

This statement, focused on melanonychia and nail plate dermoscopy, is intended to guide medical professionals working with melanonychia and to assist choosing appropriate management for melanonychia patients. The International Study Group on Melanonychia was founded in 2007 and currently has 30 members, including nail experts and dermatopathologists with special expertise in nails. The need for common definitions of nail plate dermoscopy was addressed during the Second Meeting of this Group held in February 2008. Prior to this meeting and to date (2010) there have been no evidence-based guidelines on the use of dermoscopy in the management of nail pigmentation.     

Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells

Adiponectin limits the development of liver fibrosis and activates adenosine monophosphate-activated protein kinase (AMPK). AMPK is a sensor of the cellular energy status, but its possible modulation of the fibrogenic properties of hepatic stellate cells (HSCs) has not been established. In this study, we investigated the role of AMPK activation in the biology of activated human HSCs. A time-dependent activation of AMPK was observed in response to a number of stimuli, including globular adiponectin, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), or metformin. All these compounds significantly inhibited platelet-derived growth factor (PDGF)-stimulated proliferation and migration of human HSCs and reduced the secretion of monocyte chemoattractant protein-1. In addition, AICAR limited the secretion of type I procollagen. Knockdown of AMPK by gene silencing increased the mitogenic effects of PDGF, confirming the negative modulation exerted by this pathway on HSCs. AMPK activation did not reduce PDGF-dependent activation of extracellular signal-regulated kinase (ERK) or Akt at early time points, whereas a marked inhibition was observed 24 hours after addition of PDGF, reflecting a block in cell cycle progression. In contrast, AICAR blocked short-term phosphorylation of ribosomal S6 kinase (p70(S6K)) and 4E binding protein-1 (4EBP1), 2 downstream effectors of the mammalian target of rapamycin (mTOR) pathway, by PDGF. The ability of interleukin-a (IL-1) to activate nuclear factor kappa B (NF-kappaB) was also reduced by AICAR. CONCLUSION: Activation of AMPK negatively modulates the activated phenotype of HSCs.     

Risk Factors and Comorbidities for Onychomycosis: Implications for Treatment with Topical Therapy

A number of comorbidities and risk factors complicate the successful management of onychomycosis. Underlying conditions and patient characteristics, such as tinea pedis, age, and obesity, contribute to risk, whereas comorbidities, such as diabetes and psoriasis, can increase susceptibility to the disease. There are limited data on treatment effectiveness in these patients. Here, the authors review post hoc analyses of efinaconazole topical solution, 10%, in mild-to-moderate onychomycosis and present new data in terms of age and obesity. The only post hoc analysis to report significant differences so far is gender, where female patients do much better; however, the reasons are unclear. The authors report significant differences in terms of efficacy in obese patients who do not respond as well as those with normal body mass index (P=0.05) and in patients who have their co-existing tinea pedis treated compared to those in whom co-existing tinea pedis was not treated (P=0.025). Although there is a trend to reduced efficacy in older patients and those with co-existing diabetes, differences were not significant. More research is needed in onychomycosis patients with these important risk factors and comorbidities to fully evaluate the treatment challengse and possible solutions.Onychomycosis is a common problem in dermatology practice that can result in significant morbidity.1,2 Successful treatment has been difficult because of slow growth of the nail; patient comorbidities, such as diabetes, peripheral vascular disease, and psoriasis; and reluctance of prescribers and patients to prescribe or take oral medications because of “perceived” toxicity issues.The disease can have a major impact on the individual and other family members.3-5 Dystrophic nails can cause embarrassment, affecting a patient’s self-esteem, and may have a greater impact on quality of life (QoL) than the severity of the disease itself.6 Thickened nails can also be painful, causing discomfort in walking and affecting other aspects of daily living.3A number of underlying conditions, such as tinea pedis, nail damage, and nail psoriasis can contribute to risk as well as characteristics such as age and obesity. Underlying comorbidities, such as diabetes,7,8 cancer,7,9 immunodeficiency,10 or peripheral arterial disease,11 can increase susceptibility to onychomycosis.7 An inherited genetic predisposition to infection has also been identified.12Clinical trials provide guidance on likely treatment outcomes in these patients at risk. However, some comorbid conditions (i.e., peripheral vascular disease) can be exclusion criteria, many trials were not set up to specifically study certain comorbidities, and the demographics and disposition of patients who visit dermatology and podiatry practices can be very different from those enrolled in clinical trials.Recently, a number of post hoc analyses have been published on the use of efinaconazole topical solution, 10%, in the treatment of mild-to-moderate onychomycosis. Where data exist, it is the authors’ intention to review the findings in terms of the implications for successful treatment outcomes. In addition, they present new data with efinaconazole in terms of age and obesity.Aging is the most common risk factor for onychomycosis, most likely due to poor peripheral circulation, longer exposure to pathogenic fungi, repeated nail trauma, suboptimal immune function, and slower nail growth.13 In addition, various medical conditions more common in the elderly increase the risk of comorbid onychomycosis. Surveys suggest that overall the incidence is much higher in adults than in children, afflicting 0.6 percent of children under the age of 18 years, approximately 10 to 20 percent of adults and 15 to 40 percent of elderly people.14-16 However, prevalence rates do not necessarily correlate with consultations. Not all of the patients we see with onychomycosis are elderly. This could be attributed to the fact that onychomycosis may be considered a cosmetic problem by the younger patients who are more conscious of their appearance coming forward for therapy. The increased incidence in the younger population could also be due to their exposure to occupation-related trauma predisposing them to onychomycosis or the more common use of occlusive footwear.