Association of Obesity and Bariatric Surgery on Hair Health.

Obesity and obesity-related conditions today constitute a public health problem worldwide. Obesity is an "epidemic" chronic disorder, which is defined by the WHO as normal or excessive fat accumulation that may impair health. It is also defined for adults as a BMI that is greater than or equal to 30. The most common obesity-related diseases are type 2 diabetes mellitus, cardiovascular diseases, metabolic syndrome, chronic kidney disease, hyperlipidemia, hypertension, nonalcoholic fatty liver disease, and certain types of cancer. It has been also proven that obesity can have a negative effect on hair. It can lead to hair thinning. Patients with obesity can undergo bariatric surgery if they meet the inclusion criteria. The four common types of weight loss surgery include a duodenal switch with biliopancreatic diversion, laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, and sleeve gastrectomy. Bariatric surgery can affect skin and hair and is associated with telogen effluvium due to weight loss, microelement deficiency, anesthesia, low calorie intake, and low protein intake. Patients who undergo bariatric surgery can experience post-bariatric surgery depression. Hair loss can have a major impact on self-esteem, negatively affecting one's self-image. The purpose of this narrative review is to critically review how obesity, obesity-related diseases, and bariatric surgery affect hair health in general and the hair development cycle, and how they influence hair loss.

Cognitive decline and dementia in women after menopause: Prevention strategies.

Worldwide, cognitive decline and dementia are becoming one of the biggest challenges for public health. The decline in cognition and the development of dementia may be caused by predisposing or trigger factors. There is no consensus over whether the drop in estrogen levels after menopause is a risk factor for cognitive decline and dementia. This article discusses the prevention of cognitive decline and dementia in women after menopause, both primary prevention (essentially pharmacological intervention) and secondary prevention (chiefly diet and weight reduction). Further study is required to clarify whether menopausal hormone therapy (MHT) has a role in dementia.

Lymphogranuloma venereum: an emerging problem in Poland.

Lymphogranuloma venereum (LGV) is a sexually transmitted disease that increases in incidence, particularly in more developed countries worldwide. LGV is caused by Chlamydia trachomatis serovars/genovars L1-3, including their subvariants, and in Europe mostly affects men who have sex with men (MSM). It can be asymptomatic but has now emerged as a frequent cause of severe proctitis/proctocolitis, especially in MSM. LGV has often been misdiagnosed as C. trachomatis serovars/genovars D-K infection. It is essential with accurate diagnosis that ensures appropriate treatment and protects the patient from complications and sequelae as well as from the consequences of misdiagnosis, e.g. as inflammatory bowel disease or cancer. We present a systematic review of LGV and two new LGV cases diagnosed in Poland.

Diagnostics of autoimmune blistering disorders: an experience of a single tertiary referral centre.

Autoimmune blistering disorders (AIBD) include a heterogeneous group of diseases characterized by the presence of autoantibodies against the structural antigens of the skin and mucous membranes. The gold standard of AIBD diagnostics is the detection of in vivo bound IgG/IgA and/or complement component 3 in the direct immunofluorescence of a perilesional biopsy. Various immunological techniques such as indirect immunofluorescence of different tissue substrates including monkey oesophagus, salt split skin, recombinant proteins of epidermis and basement membrane zone as well as ELISA systems and immunoblotting are used to characterize target antigens. Proper and early diagnosis is crucial for both treatment and prognosis since some AIBD may be associated with a malignant neoplasm.

Parents' Knowledge and Attitude towards HPV and HPV Vaccination in Poland.

HPV is one of the diseases of civilization that causes cervical cancer, among other diseases. For this reason, a vaccination program has been introduced worldwide for preadolescent, sexually inactive seronegative girls. However, the decision to vaccinate young girls must be made by the parents. In Poland, vaccinations are recommended but not financed by the government, which affects their choices, and there is insufficient knowledge of the diseases caused by genital HPV types. In addition, there are cultural, social, and even religious factors to be considered. Therefore, the aim of the study was to analyze the state of knowledge about HPV and HPV vaccines among parents. Two hundred and eighty-eight parents participated in the study, but only 180 of them declared that they had ever heard of HPV (62.5%). Therefore, only these parents completed the entire questionnaire consisting of 34 questions. The parents' answers were analyzed with the Fisher's and chi-squared tests. The study showed that parents' knowledge of HPV and HPV vaccination in Poland is low (49.4% of correct answers). Parents' attitudes were only influenced by knowledge and education and not by other parameters such as age, gender, place of residence, and the number of children. This study indicates that parents need to be educated about the threats of HPV and the possibilities of prophylactic vaccination.

Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.

Menopause in women with schizophrenia, schizoaffective disorder and bipolar disorder.

The transition to menopause, usually occurring between the ages of 40 and 55, is a time when women are particularly vulnerable. When preexisting mental illness is present, symptoms are often amplified during this period. Moreover, women with mental illnesses experience menopausal symptoms similarly to healthy women. In this narrative review we summarize the current data regarding menopause in women with schizophrenia, schizoaffective disorder, and bipolar disorder, as well as current standards of management and care. The management of chronic disease in women suffering from severe mental illness is also considered.

Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge.

Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4-30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave's disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto's type thyroid antibodies and has a prevalence of 10-40%. 21OH-Antibodies in Addison's disease (AD) can develop in association to APS-2.

Chronic Low Grade Inflammation in Pathogenesis of PCOS.

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5-10% in reproductive aged women. It's characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

The Impact of Selected Bacterial Sexually Transmitted Diseases on Pregnancy and Female Fertility.

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance.

Assessment of the State of Knowledge about HPV Infection and HPV Vaccination among Polish Resident Doctors.

HPV (human papillomavirus) vaccinations have been introduced into the population of many countries through vaccination programs, although their acceptance varies from country to country, largely dependent on the state of knowledge about diseases caused by genital HPV types as well as cultural, social, and religious factors. The aim of the study was to analyze the state of knowledge about HPV and HPV vaccines among doctors during their specialization in gynecology and obstetrics, dermatology and venereology, and pediatrics. Another objective of the study was to analyze the impact of the state of knowledge about HPV vaccination on their attitude to primary prevention, i.e., vaccinations. A questionnaire was used to collect the data and 639 doctors took part in the study. The analysis was carried out mainly using descriptive statistical methods. In Poland, doctors' knowledge about HPV is low, independent of gender, age, and subject of specialization. Doctors' knowledge about the HPV vaccine is very low and independent of sex, age, and subject of specialization. However, doctors' knowledge about HPV and the HPV vaccine influences the attitude to HPV vaccination and does not affect pro-active behaviors.

Hormonal Effects on Hair Follicles.

The hair cycle and hair follicle structure are highly affected by various hormones. Androgens-such as testosterone (T); dihydrotestosterone (DHT); and their prohormones, dehydroepiandrosterone sulfate (DHEAS) and androstendione (A)-are the key factors in terminal hair growth. They act on sex-specific areas of the body, converting small, straight, fair vellus hairs into larger darker terminal hairs. They bind to intracellular androgen receptors in the dermal papilla cells of the hair follicle. The majority of hair follicles also require the intracellular enzyme 5-alpha reductase to convert testosterone into DHT. Apart from androgens, the role of other hormones is also currently being researched-e.g., estradiol can significantly alter the hair follicle growth and cycle by binding to estrogen receptors and influencing aromatase activity, which is responsible for converting androgen into estrogen (E2). Progesterone, at the level of the hair follicle, decreases the conversion of testosterone into DHT. The influence of prolactin (PRL) on hair growth has also been intensively investigated, and PRL and PRL receptors were detected in human scalp skin. Our review includes results from many analyses and provides a comprehensive up-to-date understanding of the subject of the effects of hormonal changes on the hair follicle.

Correlation of Cancer Development and Human Papilloma Virus Infection in Patients After Organ Transplantation.

Immunosuppressed patients are at higher risk of developing human papilloma virus (HPV) cancerous and precancerous lesions in the anogenital region Carcinogenesis after organ transplantation due to immunosuppressive therapy is the major cause of long-term negative transplantation results. This is a rationale for the improvement of transplantation programs with carcinogenesis risk stratification in patients referred for transplantation. There is a need for a study on HPV-related carcinogenesis also in terms of its risk factors in the population after organ transplantation. This study aimed to assess the morbidity of anogenital carcinoma in patients with HPV infection, including those after organ transplantation and evaluate risk factors for carcinoma occurrence in patients after organ transplantation and with HPV infection. Our analysis directly indicates the group of patients with a high risk of HPV-related oncological complications of immunosuppression in anogenital region.

Cyto-Immuno-Therapy for Cancer: A Pathway Elicited by Tumor-Targeted, Cytotoxic Drug-Packaged Bacterially Derived Nanocells.

Immunotherapy has emerged as a powerful new chapter in the fight against cancer. However, it has yet to reach its full potential due in part to the complexity of the cancer immune response. We demonstrate that tumor-targeting EDV nanocells function as an immunotherapeutic by delivering a cytotoxin in conjunction with activation of the immune system. These nanocells polarize M1 macrophages and activate NK cells concurrently producing a Th1 cytokine response resulting in potent antitumor function. Dendritic cell maturation and antigen presentation follows, which generates tumor-specific CD8+ T cells, conferring prolonged tumor remission. The combination of cytotoxin delivery and activation of innate and adaptive antitumor immune responses results in a potent cyto-immunotherapeutic with potential in clinical oncology.

Polymetastatic testicular cancer turns out to be secondary syphilis: a case report.

Syphilis is a sexually transmissible infection, with increasing rates of infection worldwide. The differential diagnosis of syphilis should include various diseases, not excluding cancer. Making the right diagnosis can protect the patient against life-threatening complications and the repercussions of a misdiagnosis, as in the present case (orchidectomy).

Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model.

BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma.

Pathogenic activity of circulating anti-desmoglein-3 autoantibodies isolated from pemphigus vulgaris patients.

INTRODUCTION: There are scarce data on immunochemical properties of pemphigus antibodies detected in clinical remission in pemphigus vulgaris (PV) patients. The aim of the study was to compare biological activity of anti-Dsg3 autoantibodies purified from the sera of PV patients in active stage and in clinical remission. MATERIAL AND METHODS: The effect of purified antibodies on expression of procaspase-3, Bax, Bcl-2, uPAR, IL-1ß, IL-6, and TNF-α mRNAs in the HaCaT keratinocytes was evaluated by Western blot and RT-PCR method. RESULTS: Incubation of HaCaT cells with anti-Dsg-3 autoantibodies caused their binding to cell membranes surfaces. Anti-Dsg3 autoantibodies isolated from the patients in active stage and clinical remission showed proapoptotic effect, caused enhanced expression of analyzed proinflammatory cytokines' mRNAs and uPAR mRNA. CONCLUSIONS: Our data revealed similar pathogenic activity of anti Dsg-3 autoantibodies isolated from active and clinical remission PV patients.

PAK is required for the disruption of E-cadherin adhesion by the small GTPase Rac.

E-cadherin cell-cell adhesion plays a major role in the maintenance of the morphology and function of epithelial tissues. Modulation of E-cadherin function is an important process in morphogenesis and tumour de-differentiation. We have previously shown that constitutively active Rac1 induces the disassembly of E-cadherin complexes from junctions in human keratinocytes. Here, we compare this activity in three members of the Rac subfamily (Rac1, Rac3 and Rac1b) and investigate the molecular mechanisms underlying Rac1-induced destabilization of junctions. We demonstrate that Rac3 shares with Rac1 the ability to interfere with cadherin-mediated adhesion. Rac1b is an alternative splice variant of Rac1 but, surprisingly, Rac1b cannot induce junction disassembly. Thus, Rac family members differ on their potential to perturb keratinocyte cell-cell contacts. The mechanism through which Rac promotes disassembly of cadherin-dependent adhesion does not involve an increase in contractility. Instead, activation of the Rac target PAK1 is necessary for destabilization of cell-cell contacts. Inhibition of PAK1 by dominant-negative constructs or depletion of endogenous PAK1 by RNA interference efficiently blocked Rac1-induced perturbation of junctions. Interestingly, PAK1 cannot be activated by Rac1b, suggesting that this may contribute to the inability of Rac1b to disrupt cell-cell contacts in keratinocytes. As PAK1 also plays a crucial role in lamellipodia formation, our data indicate that PAK1 is at the interface between junction destabilization and increased motility during morphogenetic events.

Ku80 as a novel receptor for thymosin beta4 that mediates its intracellular activity different from G-actin sequestering.

Our data demonstrate that increased intracellular expression of thymosin beta4(Tbeta4) is necessary and sufficient to induce plasminogen activator inhibitor type 1 (PAI-1) gene expression in endothelial cells. To describe the mechanism of this effect, we produced Tbeta4 mutants with impaired functional motifs and tested their intracellular location and activity. Cytoplasmic distributions of Tbeta4((AcSDKPT/4A)), Tbeta4((KLKKTET/7A)), and Tbeta4((K16A)) mutants fused with green fluorescent protein did not differ significantly from those of wild-type Tbeta4. Overexpression of Tbeta4, Tbeta4((AcSDKPT/4A)), and Tbeta4((K16A)) affected intracellular formation of actin filaments. As expected, Tbeta4((K16A)) uptake by nuclei was impaired. On the other hand, overexpression of Tbeta4((KLKKTET/7A)) resulted in developing the actin filament network typical of adhering cells, indicating that the mutant lacked the actin binding site. The mechanism by which intracellular Tbeta4 induced the PAI-1 gene did not depend upon the N-terminal tetrapeptide AcSDKP and depended only partially on its ability to bind G-actin or enter the nucleus. Both Tbeta4 and Tbeta4((AcSDKPT/4A)) induced the PAI-1 gene to the same extent, whereas mutants Tbeta4((KLKKTET/7A)) and Tbeta4((K16A)) retained about 60% of the original activity. By proteomic analysis, the Ku80 subunit of ATP-dependent DNA helicase II was found to be associated with Tbeta4. Ku80 and Tbeta4 consistently co-immunoprecipitated in a complex from endothelial cells. Co-transfection of endothelial cells with the Ku80 deletion mutants and Tbeta4 showed that the C-terminal arm domain of Ku80 is directly involved in this interaction. Furthermore, down-regulation of Ku80 by specific short interference RNA resulted in dramatic reduction in PAI-1 expression at the level of both mRNA and protein synthesis. These data suggest that Ku80 functions as a novel receptor for Tbeta4 and mediates its intracellular activity.