Species distribution patterns and epidemiological characteristics of otomycosis in Southeastern Serbia.

INTRODUCTION: Otomycosis, a superficial fungal infection of the external auditory canal (EAC), is a disease with exceptionally high prevalence. AIM: The aim of this study was to determine the prevalence of otomycosis, the distribution of causative species and to evaluate epidemiological characteristics of these infections. METHODOLOGY: The patients' data were collected from record book and database of mycological examinations conducted at Public Health Institute Nis, Serbia. In the period from 2014 to 2018 samples of 1287 patients with symptoms and signs of EAC infection were investigated. Standard mycological methods were used for isolation and determination of fungi. RESULTS: High prevalence of otomycosis was determined in examined patients (22.7%). However, the prevalence rates did not differ significantly in the studied period (p=0.931). The majority of patients were diagnosed with only unilateral EAC infection (82.9%). Considering all patients with otomycosis, mold infections caused by the genus Aspergillus (143/48.9%) were more frequent than Candida spp. ear infections (133/45.6%), with Aspergillus niger and Candida аlbicans being predominant causative agents. Mixed Aspergillus and Candida otomycosis was established in 16 (5.5%) patients. Otomycosis was more common in male subjects (26.8%, p=0.003) who also suffered from Aspergillus otomycosis more frequently (17.5%, p<0.001). The prevalence of these infections increases with age (p=0.005), while they do not show seasonal pattern (p>0.05). CONCLUSION: Noted high prevalence of otomycosis, with both yeasts and non-dermatophyte molds acting as infectious agents which require different treatment, implies the necessity for further epidemiological monitoring of this form of superficial mycoses.

Type 2 diabetes: the genetic conflict hypothesis.

We propose that conflict between paternally and maternally derived genes in the fetus explains three apparently unrelated observations in epidemiological studies of type 2 diabetes mellitus (DM2): (i) low birth weight is a risk factor for the development of DM2, (ii) there is a high prevalence of low birth weight among babies of fathers who develop DM2, and (iii) an exceptionally high prevalence of DM2 exists in modern day Arabs. Genetic conflict is caused by a particular relationship between the parents, their genes and their offspring: (i) mothers are sometimes polyandrous i.e. have children with more than one man, (ii) mothers provide more biological resources to the fetus than fathers, and (iii) the genes that regulate fetal growth come from both parents and both sets of genes determine the use of resources which are only those of the mother. There is a tendency for maternally derived genes (that promote fetal growth) to be suppressed, in order to spare use of mother's resources, while the same paternally derived genes tend to be expressed (to enhance use of the mother's resources). These same genes are pleiotropic: they affect not only fetal growth (birth weight) but also insulin resistance and hence the development of DM2. Polyandry increases differences in the expression between two parental alleles in the fetus i.e. increases genetic conflict and results in the production of bigger babies whereas monandry has the opposite effect. Consequently, parent-of-origin-biased expression of pleiotropic developmental genes could explain why smaller babies are more common when the fathers have DM2. Similarly less genetic conflict in Arabs (resulting from the tradition of strict monandry, the practice of levirate, and preference for a paternal cousin as spouse) could explain, at least in part, their exceptionally high prevalence of DM2. This hypothesis links human mate selection with the risk of developing DM2.

On some novel aspects of consanguineous marriages.

Consanguineous marriages, often viewed as incestuous and objectionable, are more widespread than commonly perceived. They integrate multiple facets of human adaptation: economic, cultural and genetic. The widely touted explanation for the origin and persistence of consanguinity is that it provides many socioeconomic benefits; however, this view may be too simplistic. The bias against consanguinity may preclude an objective understanding of this sociobiological puzzle. Inbreeding increases the speed of selection of beneficial recessive and co-dominant alleles, e.g. those that protect against diseases. In populations endemic with malaria, the prevalence of consanguineous marriages and the frequency of alleles protective against malaria are both very high. Thus, consanguinity could theoretically increase the relative fitness of a population under specific ecological conditions; sometimes, the overall genetic benefits may exceed genetic costs of inbreeding. We discuss some recent evidence from studies on inbreeding along with the reasons responsible for the mating strategy found in some human populations. We contend that a better appreciation of our inherent biases and potential genetic benefits of inbreeding in specific ecological conditions would help us to appreciate the wider picture of consanguinity.

Robust control of uncertain context-sensitive probabilistic Boolean networks.

Uncertainty is an intrinsic phenomenon in control of gene regulatory networks (GRNs). The presence of uncertainty is related to impreciseness of GRN models due to: (1) Errors caused by imperfection of measurement devices and (2) Models' inability to fully capture a complex structure of the GRN. Consequently, there is a discrepancy between actual behaviour of the GRN and what is predicted by its mathematical model. This can result in false control signals, which can drive a cell to an undesirable state. To address the problem of control under uncertainties, a risk-sensitive control paradigm is proposed. Robustness is accomplished by minimisation of the mean exponential cost as opposed to, for instance, minimisation of the mean square cost by risk-neutral controllers. The authors derive an optimal risk-sensitive controller when a GRN is modelled by a context-sensitive probabilistic Boolean network (CSPBN). By using a relation between the relative entropy and free-energy, a relative stability of the cost achieved by the risk-sensitive controller is demonstrated when the distribution of the CSPBN attractors is perturbed, as opposed to the cost of the risk-neutral controller that exhibits increase. The use of the relation between the relative entropy and free-energy to analyse the influence of a particular attractor on the robustness of the controller is studied. The efficiency of the risk-sensitive controller is tested for the CSPBN obtained from the study of malignant melanoma.

Cancer by negative heterosis: breast and ovarian cancer excess in hybrids of inbred ethnic groups.

Breast and ovarian cancer rates in Pakistan are significantly higher than in neighboring countries. The cancer rate discrepancies cannot be explained with discrepancies of their risk factors. We propose that observed cancer excess in Pakistan is due to cancer development by negative heterosis. Heterosis occurs when a hybrid has a phenotypic characteristic significantly different from that in either parent (hybrid vigor). At a molecular level, heterosis occurs in a heterozygote when one of the two alleles is inactivated. Gene inactivation occurs by methylation of cytosine in a promoter region of a gene. Initiation of allele inactivation is linked to the factors like stress, gender, diet, or another gene. In heterozygote, inactivation of one of the two tumor-suppressor alleles leads to monoallelic expression. This increases cancer risk in the same way the risk is increased in individual who inherit a single mutated tumor-suppressor gene (hereditary cancer syndrome). In both, cancer by heterosis and inherited cancer syndrome, cancer develops after inactivation of a second allele (second hit hypothesis). In a population, conditions that favor development of cancer by heterosis are those that favor mating of a large number of different homozygotes because they produce a large number of different heterozygotes. Among a large number of heterozygotes, there is an increased chance that some of hybrids will develop cancer by heterosis. In Pakistan, conditions were favorable for cancer development by heterosis because country has a high number of different ethnic groups and brotherhoods all of which have a higher rate of homozygosity due to a high frequency of consanguineous marriages, and marriages between members of different groups occurred because of intense population mixing. Result was birth of a large number of inter-ethnic/brotherhood hybrids (heterozygotes), some of which have developed cancer by heterosis.

Consanguinity as risk factor for cervical carcinoma.

Cervical carcinoma is caused by human papillomavirus (HPV). Among the risk factors for HPV infection are having multiple sex partners and sex partners who themselves had multiple sex partners. Women married to relatives are more likely to become infected with HPV and develop cervical carcinoma. Consanguineous spouses have a mild sexual aversion to each other that leads to sex avoidance and increases likelihood of satisfying sexual desire outside the marriage. Sexual aversion develops as a result of spouses growing together in early childhood, which triggers biological imprinting of Westermarck. Westermarck's effect prevents incest in nuclear family. In consanguineous family, it extends to spouses, producing mild sexual antipathy. Because of high prevalence of consanguinity worldwide, it is important to test this hypothesis.

Consanguinity decreases risk of breast cancer--cervical cancer unaffected.

Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40-65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42 - 1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27 - 0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38 - 1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected.

Consanguinity and family history of cancer in children with leukemia and lymphomas.

BACKGROUND: In native population of the United Arab Emirates (UAE), the rate of consanguineous marriages is 50.5%. This study was designed to determine whether the rates of consanguinity and family history of cancer among the families of children with lymphoid malignancy are different from those in the general population. METHODS: The study comprised 117 patients from the whole of the country with acute lymphocytic leukemia (ALL) and Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), ranging in age from 2 to 14 years. The consanguinity rate in the study group was compared with the rate in the general population. To study family history of cancer, the authors matched patients with 117 controls. In a telephone interview, each mother was asked to provide data regarding the biologic relationship between her and her husband as well as that between both sets of grandparents; each was also asked whether any family relative had a cancer and, if so, of what type. RESULTS: Among the 69 ALL cases, 80% of families were consanguineous and 20% were nonconsanguineous. Among the 26 NHL and 22 HL cases, each group included 3 consanguineous families, 12% and 14%, respectively. The consanguinity rates for ALL, NHL, and HL were all significantly different from the 50.5% consanguinity rate in the UAE population (all three P values < 0.0001). The family history of cancer was more often positive in ALL patients than in controls (odds ratio, 2.14; confidence interval, 1.01--4.53). Overall and for each lymphoid malignancy, there was no difference in family history of cancer between consanguineous and nonconsanguineous groups of cases. CONCLUSIONS: The consanguinity rate in the families of patients with ALL is significantly higher and in those with NHL and HL significantly lower than that in the UAE population. The family history of cancer is more often positive among ALL cases than controls--consanguinity having no effect.

Longer breast-feeding and protection against childhood leukaemia and lymphomas.

The role of breast-feeding in protecting against childhood acute leukaemia and lymphomas is uncertain. We investigated this issue in a case-control study comprising 117 patients, aged 2-14 years, with acute lymphocytic leukaemia (ALL), Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL), as well as 117 controls matched for age, sex and ethnicity. Information was collected via a telephone interview of the mothers. The median duration of breast-feeding among patients was significantly shorter than among controls, 7 (range 0-23) and 10 (range 0-20) months, respectively (P<0.0001). Breast-feeding of 0-6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for ALL (OR=2.47, 95% confidence interval (CI) 1.17-5.25), HL (OR=3.75, 95% CI 0.80-18.69), NHL (OR=4.06, 95% CI 0.82-22.59), and overall (OR=2.79, 95% CI 1.54-5.05). In the patient group, there were a significantly higher number of children and people per family, and patients were of a higher birth order than controls. In multivariate analysis, breast-feeding duration continues to be an independent predictor of lymphoid malignancies (P=0.015). In conclusion, breast-feeding lasting longer than 6 months may protect against childhood acute leukaemia and lymphomas.

Knowledge, attitudes, and practices related to breast cancer screening: a survey of Arabic women.

BACKGROUND: Incorporating breast cancer screening into day-to-day clinical care leads to early diagnosis and decreases mortality. Patients' participation in screening depends on their knowledge and attitudes, other barriers, and physician behavior. METHODS: A cross-sectional questionnaire survey was conducted to evaluate knowledge, attitudes, barriers, and practices related to breast cancer screening among Arabic women. A convenience sample was selected from 1,750 women aged 40-65 years who, for any reason, attended primary health care (PHC) clinics in Al-Ain, United Arab Emirates (UAE). RESULTS: Of the 1,750 invited women, 1,445 agreed to participate; 78 were excluded from analysis because of histories of breast cancer. Breast self-examination (BSE) was practiced by 12.7% of the study population, clinical breast examination (CBE) by 13.8%, and mammography by 10.3%. Knowledge about breast cancer screening was low in the study population. Women were infrequently instructed about or offered screening for breast cancer by health professionals. Being employed was an independent predictor for participation in the three screening examinations. CONCLUSIONS: Health workers infrequently offered screening examinations and women lacked adequate knowledge about breast cancer screening. Acquired information about barriers to screening may help in the design of effective screening programs for Arabic women.

Preoperative treatment of advanced skin carcinoma with cisplatin and bleomycin.

In advanced skin carcinomas of the head and neck region, the tumor may be unresectable or curative resection or radiation may either fail or produce poor functional and cosmetic results. The goal of this study was to test the ability of preoperative chemotherapy to decrease the extent of needed resection and tumor response. Five patients, three with squamous cell carcinoma and two with basal cell carcinoma, were treated before surgery with three cycles of cisplatin 20 mg/m2 daily for 4 days and bleomycin 20 mg/day for 4 days by continuous infusion every 3 weeks. All patients had advanced cancer in the head and neck region, one had unresectable tumor, two had xeroderma pigmentosum, and one was a 13-year-old child. The history of prior treatments was as follows: radiation therapy (n = 3), systemic chemotherapy (n = 1), surgery (n = 1), and no treatment (n = 1). One patient had complete clinical but not pathologic response, three had partial response, and one had progressive disease. The extent of resection after chemotherapy was dramatically reduced in the patient with a complete response and minimally changed in the patients with partials responses and progressive disease. All patients who underwent surgery became tumor free. Preventable toxicity was symptomatic hypomagnesemia in one patient, reversible elevation of creatinine in one patient, and mild nausea and vomiting in three patients. With this report, the total number of patients with nonmelanoma skin cancer who were treated with cisplatin is 68, and their overall response is 80%. Only 16 reported patients were treated with preoperative chemotherapy, and study of this treatment approach to advanced skin cancer should be pursued.

Frequency and management of germ-cell tumors in a third-world country.

Since 1977, advances in the treatment of germ-cell tumors have resulted in a declining mortality from testicular cancer. Simultaneously, a rising incidence of disease was seen in many developed parts of world. However, the frequency of and mortality from testicular cancer have not been reported from any third-world country, where larger and younger populations at risk reside. The age-specific annual incidence of testicular cancer was calculated from information in the cancer registry of Iraq (1986-1988). The data on management of 29 patients with testicular (n=15) and non-testicular (n=14) germ-cell tumors were retrospectively analyzed (9% of all non-seminoma testicular cancers in the country for the 1984-1990 period). The annual incidence of testicular cancer is low in Iraq. Transscrotal biopsy and transscrotal orchiectomy were frequently performed but did not adversely affect patient outcome. A poor outcome was associated with the lack of surveillance after surgery; inappropriate sequencing of chemotherapy, surgery and radiation treatment; and chemotherapy of a low-dose intensity. Tumor marker studies were infrequently done. In conclusion, the annual incidence of testicular carcinoma in this developing country is low, but mortality appears high due to the incomplete penetration of the current medical knowledge into clinical practice.

Three-dimensional survival model of breast cancer patients.

The established view point of survival in breast cancer patients is in terms of disease-free survival (DFS). This may be imprecise because a patient with early disease may have three different DFSs: First, from initial diagnosis until local recurrence; Second, from successful treatment of local recurrence until development of metastatic disease; Third, from complete remission of metastatic disease until recurrence of cancer. To include all three DFSs in a single model, we propose a three-dimensional survival surface for breast cancer patients. The survival surface is given as the function of tumor size and number of lymph nodes involved. The survival surface has the cusp geometry that is known to be the only stable structure for a system with two input parameters (tumor size and involved lymph nodes) and one output (DFS). The model casts new light on some views about breast cancer.

Observations supporting the existence of true local metastases of cancer.

We propose the hypothesis that around a main invading tumor, there are local metastases in the surrounding tissue/organ. They occur as a result of cancer cell migration through the interstitial matrix and we call them true local metastases. They are composed of individual or nested cells but are difficult to identify because of their nonspecific appearance, close location to the irregular surface of the main tumor and observer's inability to deduce a three dimensional structure from a few two-dimensional histological pictures. The propensity of neoplasms to locally metastasize may vary greatly among different types and stages of tumors. Better knowledge of a tumor's three dimensional spread may influence treatment strategy.

Adult T-cell leukemia/lymphoma in Brooklyn.

Fifteen patients with adult T-cell leukemia/lymphoma (ATLL) were identified in less than a two-year period in the Crown Heights-Bedford Stuyvesant section of Brooklyn, NY. All patients were black; nine patients originated from the Caribbean islands and six from the southern United States. Two of the patients were father and daughter, the first evidence of familial occurrence in the United States. Their clinical course was similar to that of previously described patients with this disorder. To our knowledge, these 15 patients represent the largest series of ATLL reported in the United States. We recommend that ATLL be seriously considered in the differential diagnosis of patients with non-Hodgkin's lymphoma, mycosis fungoides, lymphatic leukemia, or hypercalcemia.

The first report of familial adult T-cell leukemia lymphoma in the United States.

Two patients, a daughter and her father, developed the acute type of adult T-cell leukemia/lymphoma (ATLL) within a 3-month period. Antibodies against HTLV-I have been found in both wives of the father. The second wife acquired the infection from her husband within 3 years of marriage. The patients described represent the first cases of familial ATLL in the United States. ATLL continues to be frequently misdiagnosed in the United States. A positive family history consistent with this disease in a patient with a lymphoid malignancy may be a helpful clue for earlier diagnosis.