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Huntington's disease is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling Huntington's disease is challenging, as rodent and cellular models poorly recapitulate the disease as seen in ageing humans. To address this, we generated induced neurons through direct reprogramming of human skin fibroblasts, which retain age-dependent epigenetic characteristics. Huntington's disease induced neurons (HD-iNs) displayed profound deficits in autophagy, characterized by reduced transport of late autophagic structures from the neurites to the soma. These neurite-specific alterations in autophagy resulted in shorter, thinner and fewer neurites specifically in HD-iNs. CRISPRi-mediated silencing of HTT did not rescue this phenotype but rather resulted in additional autophagy alterations in control induced neurons, highlighting the importance of wild-type HTT in normal neuronal autophagy. In summary, our work identifies a distinct subcellular autophagy impairment in adult patient derived Huntington's disease neurons and provides a new rationale for future development of autophagy activation therapies.

The etiology of most neurological disorders is poorly understood and current treatments are largely ineffective. New ideas and concepts are therefore vitally important for future research in this area. This review explores the concept that dysregulation of transposable elements (TEs) contributes to the appearance and pathology of neurodevelopmental and neurodegenerative disorders. Despite TEs making up at least half of the human genome, they are vastly understudied in relation to brain disorders. However, recent advances in sequencing technologies and gene editing approaches are now starting to unravel the pathological role of TEs. Aberrant activation of TEs has been found in many neurological disorders; the resulting pathogenic effects, which include alterations of gene expression, neuroinflammation, and direct neurotoxicity, are starting to be resolved. An increased understanding of the relationship between TEs and pathological processes in the brain improves the potential for novel diagnostics and interventions for brain disorders.

The presence of penile metastatic lesions proceeding from primary rectal tumors is a rare entity usually associated with a poor prognosis. Clinical presentation and localization may vary. There exists no consensus gold standard treatment for penile metastatic lesions, and there is continuous debate on whether lesions should undergo surgical, chemotherapeutic or palliative management.

Coccidioidomycosis is an endemic disease of arid regions in the Western hemisphere. Its clinical presentation varies from asymptomatic nodules on chest x-rays to disseminated disease. We present the case of a 48-year-old man with a hard and heterogeneous tumor in the posterior aspect of the right testis. Color flow doppler testicular ultrasonography was performed and two nodular masses in the tail of the right epididymis were identified. An epididymectomy was performed and histopathological examination revealed coccidioidomycosis. After diagnosis, the patient was successfully treated with fluconazol.

The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18. ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis-acting structural variation establishes a regulatory network that affects human brain evolution.

Metabolic syndrome (MS) has been associated with testicular damage. Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease that affects different organs, but its effect on the testes is unknown. A study analyzing germ cell involvement on BALB/c mice was carried out. A parallel comparative study was conducted that investigated alterations in the germinal epithelium of male humans that died from an unrelated acute event. The complete medical histories and histologic samples of the thoracic aorta, liver tissue, and testicular tissue from the deceased subjects were collected. The degree of germinal epithelial loss (DGEL) was evaluated and the clinical and histologic data were compared between individuals with and without NAFLD. The only metabolic or morphologic variable that caused a significant difference in the DGEL, in both the animal model and humans, was the presence of liver steatosis. The percentage of steatosis was also correlated with the percentage of the DGEL. In humans, steatosis (greater than 20%) increased the risk 12-fold for presenting with a severe DGEL (OR: 12.5; 95% CI [1.2, 128.9]; p = .03). There was no association with age above 50 years or MS components. Steatosis grade was also correlated with atherosclerosis grade. NAFLD was a strongly associated factor implicated in severe DGEL, as well as the testis was identified as a probable target organ for damage caused by the disease. This finding could result in the search for new approach strategies in the management of men with fertility problems. Further studies are required to confirm these results.

Background Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. Methods DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy–Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. Results We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13–3.51, TT vs. GG; OR, 1.53; 95% CI 1.12–2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. Conclusions Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.

Background Male EBP disorder with neurologic defects (MEND) syndrome is an X‐linked disease caused by hypomorphic mutations in the EBP (emopamil‐binding protein) gene. Modifier genes may explain the clinical variability among individuals who share a primary mutation. Methods We studied four males (Patient 1 to Patient 4) exhibiting a descending degree of phenotypic severity from a family with MEND syndrome. To identify candidate modifier genes that explain the phenotypic variability, variants of homeostasis cholesterol genes identified by whole‐exome sequencing (WES) were ranked according to the predicted magnitude of their effect through an in‐house scoring system. Results Twenty‐seven from 105 missense variants found in 45 genes of the four exomes were considered significant (−5 to −9 scores). We found a direct genotype–phenotype association based on the differential accumulation of potentially functional gene variants among males. Patient 1 exhibited 17 variants, both Patients 2 and 3 exhibited nine variants, and Patient 4 exhibited only five variants. Conclusion We conclude that APOA5 (rs3135506), ABCA1 (rs9282541), and APOB (rs679899 and rs12714225) are the most relevant candidate modifier genes in this family. Relative accumulation of the deficiencies associated with variants of these genes along with other lesser deficiencies in other genes appears to explain the variable expressivity in MEND syndrome.

Background Teratomas are a spectrum of neoplasms that can undergo malignant transformation. In the World Health Organization (WHO) classification of tumors, this entity was classified as “teratoma with somatic-type malignancy”, was defined as a malignant neoplasm of non-germinal phenotype that originates in a teratoma. Materials and methods We present a series of nine cases of testicular teratomas with secondary malignant transformation. From January 1995 to December 2011, we found a total of 306 cases of testicular tumors. Mixed germ cell tumors were the most frequently diagnosed malignancy with 45.7%. Results Teratoma with secondary malignant transformation, represented 2.9% of all germinal tumors. Five cases originated within a mixed germ cell tumor, two cases from mature teratomas, and two from immature teratomas. The predominante malignant somatic component were sarcomas; two cases of chondrosarcoma, one rhabdomyosarcoma, and one case showing foci of chondrosarcoma and rhabdomyosarcoma. The case of osteosarcoma is notable for its rarity. Two cases showed epithelial malignancy in the form of an adenocarcinoma, and finally, two cases were primitive neuroectodermal tumors. At the time of diagnosis, five patients had metastases. Conclusion The transformation of germ cell tumors to somatic type malignancies is rare. The malignant component can originate from any of the three germ lines. These tumors are resistant to standard chemotherapy for a germ cell tumor and the clinical stage is the most important prognostic factor. At our institution, the malignant component that appeared most frequently was chondrosarcoma.

A phase I-II study to evaluate gene-mediated cytotoxic immunotherapy in newly diagnosed prostate cancer before radical prostatectomy was conducted in Monterrey, Mexico. First, to investigate delivery of adenovirus to the prostate, fluorescently labeled vector was injected into fresh prostatectomy specimens and distribution was visually analyzed. The optimal volume and site instillation was then used for transrectal ultrasound guided intraprostatic injection in 10 patients with adenocarcinoma scheduled for radical prostatectomy. Each received two apical and two basal 0.5 ml injections of AdV-tk for a total of 1 × 10(11) vp followed by 14 days of prodrug. Nine patients continued to tumor resection: six high risk, one intermediate and two low risk. In vivo vector distribution was analyzed from the resected tissue of four patients. Patients were monitored for tumor progression and acute and long-term safety. For vector delivery, two apical and two basal injections of 0.5 ml led to optimal organ-wide distribution ex vivo and in vivo. Cytotoxicity was evidenced by transient rise in PSA and tumor histology. There were no significant adverse events deemed related to the treatment and no late toxicities after median follow-up of 11.3 years. All six high-risk patients had positive surgical margins and one had seminal vesicle involvement. Despite slow PSA rise post surgery in three of these patients, none developed metastases. The intermediate- and low-risk patients had complete resections and none have progressed. In conclusion, in vivo transrectal ultrasound guided instillation of an adenoviral vector into four sites in the prostate was practical as an outpatient procedure, well tolerated and led to distribution throughout the intraprostatic tumor mass. AdV-tk demonstrated no significant acute or late toxicities. Trends in PSA and disease progression conveyed the possibility of a sustained immune response against residual disease.

since 1929, the imprint cytology has a great value in the transoperatory as a diagnostic tool and in some cases as an alternate method.during two years period, 416 transoperatory specimens and 384 frozen sections were performed in the Pathology and Cytopathology Department of the University Hospital, "Dr. José E. Gonzalez." Diagnoses were recorded and compared both methods with the final diagnosis given at definitive histological sections. The results were evaluated and p statistics were performed.nine of 416 patients (2.2 %) were incorrectly diagnosed by cytology, and 8 of 384 (2.1 %) by frozen section. The diagnostic accuracy for the imprint cytology was 97.8 % and 97.9 % for frozen section. Six of the 416 cases (1.4 %) were misdiagnosed by imprints and frozen sections; the percentage success was 98.5 % using both methods together. The p was statistically significant (0.0005).the transoperatory cytology is a fast, easy and inexpensive. It provides morphological detail on intact cells and without the freezing artifacts, so its use as an adjunct to the frozen method is of great value.

The gynandroblastoma is an extremely rare sexual cord stromal tumor, which contains both male and female elements, characterized by Sertoli or Leydig cells and granulose cells. We describe an ovarian gynandroblastoma in a 28 year-old female patient, found accidentally during a cesarean section operation. There is only one reported case in world literature occurring in a pregnant woman. The principal component we found was adult granulose cells, with a microfollicular pattern, and the presence of luteinized cells in some areas; besides we found the presence of well differentiated Sertoli cells elements, in addition to Leydig cells groups, in over 10% of the tumoral surface. Inmunohistochemical stainings were performed: citokeratin, which resulted positive in Sertoli cells and negative in granulose cells; and inhibin, which was positive in both components showing its mixed origin.

Metastasis to the umbilicus, known as Sister Mary Joseph's nodule, sometimes represents the first clinical manifestation of an internal malignancy. These nodules are infrequent, and their discovery has prognostic implications.An 86-year-old woman presented with an ultrasound diagnosis of peritoneal carcinomatosis and the presence of a round lesion in the umbilical area. A fine needle aspiration biopsy was performed. The cytologic smears showed a biphasic neoplasm composed of malignant epithelial cells with a glandular appearance and randomly scattered spindle cells in a necrotic base. Immunohistochemical staining was performed to confirm the diagnosis.After an extensive search of the literature, we discovered that this is the first report of a metastatic carcinosarcoma diagnosed by fine needle aspiration biopsy. The diagnosis of carcinosarcoma requires a clear definition of the 2 components, which is why immunohistochemical staining is very useful. The presence of an umbilical nodule should raise suspicion of an underlying malignant neoplasm. Needle aspiration biopsy should be considered as the most effective, simple, uncomplicated method of diagnosing these lesions.

Background Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs), and human cytomegalovirus (HCMV) infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV) was identified in prostate tissue with a high prevalence observed in prostate cancer (PC) patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q). Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. Methods 130 subjects (55 prostate cancer cases and 75 controls) were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. Results R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0%) cases and 4 (5.3%) controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027) by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. Conclusions We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.

Background Prostate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico. Methods After receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB). Results A total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores ≥ 7. Conclusion Our results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason ≥ 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns.

Fine needle aspiration biopsy (FNAB) of the skin is useful in subcutaneous lesions. Dermatophytes are almost exclusively superficial cutaneous mycoses and constitute 70-80% of all mycoses and 5% of dermatologic consultations. Inflammatory and invasive forms, as well as infections that remain in chronic forms or persist in spite of treatment, are more frequent in immunocompromised individuals. The clinicalpresentations of these invasive cases are dermatopbytic granulomas (granuloma of Wilson-Majocchi and pseudomycetoma) or Hadida's disease.A 17-year-old male with an 8-year history of tinea capitis and multiple kerion lesions in the occipital region, left foot and right elbow resistant to conventional treatment was diagnosed by KOH tests and cultures as Microsporum canis. Two months before consultation he noticed the slow growth of a subcutaneous nodule in the base of the neck. FNAB of the neck nodule was performed. The diagnosis of pseudomycetoma by Microsporum canis was made.We report a case of pseudomycetoma caused by Microsporum canis, with the diagnosis made by FNAB. This case appears to be the first one diagnosed by this method in a human.

Atypical mycobacteriosis of the duodenum was diagnosed by duodenal brush cytology in a woman with AIDS. Smears were fixed in alcohol and stained by the method of Papanicolaou. The cytological characteristics of this disease have been described previously in other cytological specimens such as imprints or fine-needle aspirations stained with Diff-Quik or Wright's stain. We found that alcohol fixation and routine Papanicolaou staining allow observation of numerous foamy and striated macrophages (pseudo-Gaucher cells), as well as negative images both within the cytoplasm of the macrophages and in the background of smears in areas of air-drying artifact. These findings should suggest the diagnosis of atypical mycobacteriosis, and special staining techniques such as PAS and Ziehl-Neelsen are useful in corroborating it. This has not been previously described.

Background The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. Objective The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. Methods OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. Results OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human’s orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. Conclusions Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.