Temperature Differences Between Controlled Primary Hypothyroidism and Healthy Patients: An Exploratory Study.

Introduction: Hypothyroidism is conventionally treated with replacement therapy through levothyroxine (LT4). Despite the improvement in symptoms, cold intolerance persists in some patients. The present study aims to determine whether there is a difference in temperature perception and skin temperature between patients with primary controlled hypothyroidism (PCH) and a group of healthy controls matched for body mass index and age. Secondarily we aimed to determine difference in quality of life. Methodology: Skin temperature measurements were performed in both groups, both in the central and peripheral regions of the body. In addition, subjects were asked about their perception of temperature in a temperature-controlled room; anthropometric measurements were taken, their quality of life was assessed using the ThyPRO-39, and a thyroid hormone profile was performed. Results: Eleven patients in the PCH group and 30 patients in the control group were studied. It was found that the group with PCH presented a significantly lower palmar temperature than the control group [mean (SD) of 32.05 (1.79) vs 33.10 (1.30) oC, P = .046]. A mediation model showed a direct effect. Temperature perception was equal between groups. The median (interquartile range) of ThyPRO was 8 (5.2) points in the control group vs 21.8 (13.5) in the group of controlled hypothyroidism, P < .001. Discussion: These results suggest that, despite LT4 treatment, patients continue to present abnormalities in thermogenesis-related thermogenesis, and this may be due to a lack of hormonal adaptation to environmental changes and physiological demands, leading to lower body temperatures and increased sensitivity to cold.

Closed reduction evaluation in dysplastic hip with the Ömeroglu system in children aged 24 to 36 months.

Closed reduction (CR) as an initial treatment for developmental hip dysplasia of the hip (DDH) in children aged 24 to 36 months is debatable; however, it could have better results than open reduction (OR) or osteotomies, because it is minimally invasive. The purpose of this study was to evaluate the radiological results in children (24-36 months) with DDH initially treated with CR. Initial, subsequent, final anteroposterior pelvic radiological records were retrospectively analyzed. The International Hip Dysplasia Institute was used to classify the initial dislocations. To evaluate the final radiological results after CR (initial treatment) or additional treatment (CR failed), the Ömeroglu system was used (6 points excellent, 5 good, 4 fair-plus, 3 fair-minus, and ≤2 poor). The degree of acetabular dysplasia was estimated using the initial acetabular index and the final acetabular index, Buchholz-Ogden classification was used to measure avascular necrosis (AVN). A total of 98 radiological records were eligible, including 53 patients (65 hips). Fifteen hips (23.1%) were redislocated, OR with femoral osteotomy and pelvic osteotomy was the preferred surgical treatment 9 (13.8%). The initial acetabular index versus final acetabular index in total population was (38.9º ± 6.8º) and (31.9º ± 6.8º), respectively (t = 6.5, P < .001). The prevalence of AVN was 40%. Overall AVN in OR, femoral osteotomy and pelvic osteotomy were 73.3% versus CR 30%, P = .003. Unsatisfactory results ≤ 4 points on the Ömeroglu system were observed in hips that required OR with femoral and pelvic osteotomy. Hips with DDH treated with CR initially might had better radiological results than those treated with OR and femoral and pelvic osteotomies. Regular, good, and excellent results, ≥4 points on the Ömeroglu system, could be estimated in 57% of the cases, in whom CR was successful. AVN is frequently observed in hips with failed CR.

Postaxial hypoplasia of the lower extremity associated with congenital dislocation of the patella: A case report.

RATIONALE: Evaluation of clinical and radiologic abnormalities in patients with postaxial hypoplasia of the lower extremity (PHLE) for treatment decisions represents a major challenge, which is more complicated when PHLE is associated with congenital dislocation of the patella. PATIENT CONCERNS: : Herein, we present the case of an 8-year-old female patient with evident length inequality in her left lower extremity and inability to walk. DIAGNOSES: Radiological evaluation revealed PHLE with fibular hemimelia, proximal femoral focal deficiency, tarsal coalition, and congenital patellar dislocation of the patella. The right lower extremity was also affected by fibular hemimelia. INTERVENTIONS AND OUTCOMES: Surgical management included the Roux-Goldthwait technique for patellofemoral joint realignment, a medial knee stapled with Blount technique, and femur enlargement using the Wagner technique. The results from surgical intervention included a left femoral elongation of 6.7 cm featuring callus with angulation, displacement, and a discrepancy of 5 cm between femurs with a flexor contraction in the knee of -15° and a centralized knee. LESSON: PHLE accompanied by congenital dislocation of the patella has not been extensively described in the literature; therefore, there is no established management. Starting reconstruction at an early age, together with an adequate classification of the deformity, are essential factors when opting for limb reconstruction.

Survival at 30 days in elderly patients with hip fracture surgery who were exposed to hypothermia: Survival study.

ABSTRACT: The effect of hypothermia as a mortality risk factor at 30 days in the elderly who had hip fracture (HF) surgery is still controversial because it may be due to a set of poorly identified factors. In this study, we aim to determine if exposure to intra and immediate postoperative hypothermia increases the incidence of mortality at 30 days in elderly patients who had HF surgery.Survival study in the elderly who had HF surgery with and without exposure to hypothermia. Sociodemographic, anesthetic and surgical factors were collected. The temperature of the rectum was measured at the end of the surgery and in the recovery room. The effect of hypothermia was analyzed by the incidence of mortality at 30 days. Other results were considered, such as, surgical site infection (SSI), blood transfusions, and influence of implants used in the 30-day mortality.Three hundred eighty five subjects were eligible, to include 300. Inadvertent hypothermia was 12%, the 30-day overall mortality was 9% and in subjects with hypothermia it was 25% (P = .002). Subjects with hypothermia had a higher risk of SSI (relative risk 4.2, 95% confidence interval 1.3-13.6, P = .03) and receive more transfusions (relative risk 3.6, 95% confidence interval 2.0-6.5, P < .001).Elderly subjects with HF exposed to hypothermia who undergo hip hemiarthroplasty and who receive 2 or more blood transfusions during their treatment, are at greater risk of dying after 30 days of the surgery. Hypothermia, as a possible causative factor of mortality, should continue to be studied.

SeXY chromosomes and the immune system: reflections after a comparative study.

BACKGROUND: Sex bias in immune function has been contributed in part to a preponderance of immune system-related genes (ISRG) on the X-chromosome. We verified whether ISRG are more abundant on the X chromosome as compared to autosomal chromosomes and reflected on the impact of our findings. METHODS: Consulting freely accessible databases, we performed a comparative study consisting of three complementary strategies. First, among coding X/Y-linked genes, the abundance of ISRG was compared to the abundance of genes dedicated to other systems. Genes were assigned considering three criteria: disease, tissue expression, and function (DEF approach). In addition, we carried out two genome-wide approaches to compare the contribution of sex and autosomal chromosomes to immune genes defined by an elevated expression in lymphatic tissues (LTEEG approach) or annotation to an immune system process, GO:0002376 (GO approach). RESULTS: The X chromosome had less immune genes than the median of the autosomal chromosomes. Among X-linked genes, ISRG ranked fourth after the reproductive and nervous systems and genes dedicated to development, proliferation and apoptosis. On the Y chromosome, ISRG ranked second, and at the pseudoautosomal region (PAR) first. According to studies on the expression of X-linked genes in a variety of (mostly non-lymphatic) tissues, almost two-thirds of ISRG are expressed without sex bias, and the remaining ISRG presented female and male bias with similar frequency. Various epigenetic controllers, X-linked MSL3 and Y-linked KDM5D and UTY, were preferentially expressed in leukocytes and deserve further attention for a possible role in sex biased expression or its neutralisation. CONCLUSIONS: The X chromosome is not enriched for ISRG, though particular X-linked genes may be responsible for sex differences in certain immune responses. So far, there is insufficient information on sex-biased expression of X/Y-linked ISRG in leukocytes to draw general conclusions on the impact of X/Y-linked ISRG in immune function. More research on the regulation of the expression X-linked genes is required with attention to 1) female and male mechanisms that may either augment or diminish sex biased expression and 2) tissue-specific expression studies.

Inhibitory Effect of Cuphea aequipetala Extracts on Murine B16F10 Melanoma In Vitro and In Vivo.

Cuphea aequipetala (C. aequipetala) has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of C. aequipetala on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. In vitro assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells. In vivo, groups of C57BL/6 female mice were subcutaneously injected with 5x105 B16F10 cells and treated with 25 mg/mL of C. aequipetala extracts via oral. Aqueous and methanolic extracts showed a cytotoxic effect in MCF-7, HepG2, and B16F10 cell lines. The methanolic extract showed more antiproliferative effect with less concentration, and for this reason, the in vitro experiments were only continued with it. This extract was able to induce accumulation of cells on G1 phase of the cell cycle; moreover, it was able to induce DNA fragmentation and increase the activity of caspase-3 in B16F10 cells. On the other hand, in the murine model of melanoma, the aqueous extract showed a greater reduction of tumor size in comparison with the methanolic extract, showing an 80% reduction versus one of around 31%, both compared with the untreated control, indicating a better antitumor effect of C. aequipetala aqueous extract via oral administration. In conclusion, the in vitro data showed that both C. aequipetala extracts were able to induce cytotoxicity through the apoptosis pathway in B16F10 cells, and in vivo, the oral administration of aqueous extract reduces the melanoma tumoral mass, suggesting an important antitumoral effect and the perspective to search for effector molecules involved in it.

WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma.

The global incidence of melanoma is increasing. Mortality from melanoma is influenced primarily by metastasis in advanced stages of the disease. Current treatments are largely ineffective; thus, novel gene delivery approaches that target tumor-specific markers may be useful for the treatment of melanoma. Systemic administration of encapsulated RNA-interference plasmids targeted against tumor cells is a potential alternative therapy for cancer. Formulations of transferrin (Tf)-conjugated polyethylene glycol (PEG) liposomes loaded with short hairpin RNA (shRNA) against WT1 (Lip + RNAi + Tf), PEG liposomes loaded with shRNA against WT1 (Lip + RNAi), Tf-conjugated PEG liposomes loaded with pEGFP-N3 (Lip + GFP + Tf) and saline solution as negative control (untreated) were administered systemically to C57BL/6 mice implanted subcutaneously with a melanoma cell line. Tumor volume, body weight, tumor weight, survival and relative expression of WT1 were evaluated. No significant differences in net body weight were identified between groups. The tumor volume decreased from 7,871 mm3 (SD±2,087) in the untreated group to 5,981 mm3 (SD±2,099) in the Lip + RNAi + Tf group. The tumor weight was reduced, from 8.8 g (SD±0.30) in the untreated group to 5.5 g (SD±0.87) in the Lip + RNAi + Tf group. An increase of 37% in survival was also observed in the group treated with Lip + RNAi + Tf in comparison to the untreated group. Tumors treated with Lip + RNAi + Tf also showed a decrease in the mean relative expression of WT1 of 0.21 (SD±0.28) folds compared with 1.8 (SD±2.49) folds in untreated group, 1.34 (SD±0.43) folds in Lip + RNAi group and of 1.89 (SD±0.69) folds in Lip + GFP + Tf group. Systemic administration of transferrin-conjugated PEG liposomes loaded with shRNA against WT1 reduced WT1 expression and tumor size and increased survival.

CD133 antisense suppresses cancer cell growth and increases sensitivity to cisplatin in vitro.

The increased incidence of cancer in recent years is associated with a high rate of mortality. Numerous types of cancer have a low percentage of CD133(+) cells, which have similar features to stem cells. The CD133 molecule is involved in apoptosis and cell proliferation. The aim of this study was to determine the biological effect of CD133 suppression and its role in the chemosensitization of cancer cell lines. RT-PCR and immunocytochemical analyses indicated that CD133 was expressed in the cancer cell lines B16F10, MCF7 and INER51. Downregulation of CD133 by transfection with an antisense sequence (As-CD133) resulted in a decrease in cancer cell viability of up to 52, 47 and 22% in B16F10, MCF-7 and INER51 cancer cell lines, respectively. This decreased viability appeared to be due to the induction of apoptosis. In addition, treatment with As-CD133 in combination with cisplatin had a synergic effect in all of the cancer cell lines analyzed, and in particular, significantly decreased the viability of B16F10 cancer cells compared with each treatment separately (3.1% viability for the combined treatment compared with 48% for 0.4 µg As-CD133 and 25% for 5 ng/µl cisplatin; P<0.05). The results indicate that the downregulation of CD133 by antisense is a potential therapeutic target for cancer and has a synergistic effect when administered with minimal doses of the chemotherapeutic drug cisplatin, suggesting that this combination strategy may be applied in cancer treatment.

WT1 silencing by RNAi synergizes with chemotherapeutic agents and induces chemosensitization to doxorubicin and cisplatin in B16F10 murine melanoma cells.

The Wilm's tumor gene (WT1), encoding a transcription factor that modulates the expression of certain genes that are involved in proliferation and apoptosis, is overexpressed in numerous solid tumors. WT1 is important for cell proliferation and in the diagnosis of melanoma. The objectives of this study were to investigate whether WT1 silencing is capable of synergizing with chemotherapeutic agents and whether this silencing is capable of sensitizing cancer cells to doxorubicin and cisplatin in the B16F10 murine melanoma cell line. In the present study, B16F10 cells were simultaneously treated with median lethal doses (LD50s) of WT1-1 or WT1-2 small hairpin RNAs (shRNAs) and chemotherapeutic agents. A total of 24 h post-transfection, a [3-(4,5-dimethylthiazol-2yl)-2,5- diphenyl tetrazolium bromide assay] MTT assay was performed. To determine whether shRNA interference (shRNAi) is capable of sensitizing B16F10 cells to chemotherapeutic agents, cells were transfected with an LD50 of each of the recombinant plasmids, treated with varying concentrations of doxorubicin or cisplatin 24 h post-transfection, and analyzed 48 h later for inhibition of cell proliferation using the MTT assay. We observed that WT1-RNAi and the two chemotherapeutic agents acted synergistically to inhibit B16F10 cell proliferation. The greatest inhibition of cell proliferation was observed with the WT1-2/cisplatin (91%) and WT1-1/cisplatin combinations (85%). WT1 silencing using shRNAi induced the chemosensitization of cells to doxorubicin and cisplatin, with the greatest inhibition (85%) of cell proliferation being observed in the cells treated with the WT1-2/cisplatin 6 ng/µl combination. Our results provide direct evidence that WT1 gene silencing has a synergistic effect with chemotherapeutic drugs and sensitizes B16F10 melanoma cells to doxorubicin and cisplatin. This suggests that these combination strategies are potentially utilized in melanoma therapy.