Dedifferentiated liposarcoma of the spermatic cord.

A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial presentation, the patient was found to have dedifferentiated liposarcoma (LPS) of the spermatic cord. LPS of the spermatic cord is a rare entity; however, clinicians should have LPS on the differential diagnosis especially in men with recurrent scrotal pain and mass. If unrecognised, LPS is associated with a high degree of morbidity and mortality. LPS can be subdivided into well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS. In patients with advanced or metastatic LPS, chemotherapy consisting of Adriamycin, ifosfamide and mesna is used despite LPS being relatively chemoresistant. Therapies inhibiting mouse double minute 2 homologue, an oncoprotein that is a negative regulator of the tumour suppressor p53, appear to be promising in preclinical trials.

mTOR inhibition abrogates human mammary stem cells and early breast cancer progression markers.

BACKGROUND: Mammary physiology is distinguished in containing adult stem/progenitor cells that are actively amending the breast tissue throughout the reproductive lifespan of women. Despite their importance in both mammary gland development, physiological maintenance, and reproduction, the exact role of mammary stem/progenitor cells in mammary tumorigenesis has not been fully elucidated in humans or animal models. The implications of modulating adult stem/progenitor cells in women could lead to a better understanding of not only their function, but also toward possible breast cancer prevention led us to evaluate the efficacy of rapamycin in reducing mammary stem/progenitor cell activity and malignant progression markers. METHODS: We analyzed a large number of human breast tissues for their basal and luminal cell composition with flow cytometry and their stem and progenitor cell function with sphere formation assay with respect to age and menopausal status in connection with a clinical study (NCT02642094) involving a low-dose (2 mg/day) and short-term (5-7 days) treatment of the mTOR inhibitor sirolimus. The expression of biomarkers in biopsies and surgical breast samples were measured with quantitative analysis of immunohistochemistry. RESULTS: Sirolimus treatment significantly abrogated mammary stem cell activity, particularly in postmenopausal patients. It did not affect the frequency of luminal progenitors but decreased their self-renewal capacity. While sirolimus had no effect on basal cell population, it decreased luminal cell population, particularly in postmenopausal patients. It also significantly diminished prognostic biomarkers associated with breast cancer progression from ductal carcinoma in situ to invasive breast cancer including p16INK4A, COX-2, and Ki67, as well as markers of the senescence-associated secretary phenotype, thereby possibly functioning in preventing early breast cancer progression. CONCLUSION: Overall, these findings indicate a link from mTOR signaling to mammary stem and progenitor cell activity and cancer progression. Trial registration This study involves a clinical trial registered under the ClinicalTrials.gov identifier NCT02642094 registered December 30, 2015.

Oedema: a rare complication of plasma donation in an adolescent female.

Plasma donation has been widely used to recover medically vital components, such as immunoglobulins and clotting factors. Although generally well tolerated, there have been reports in the medical literature of reactions following blood and plasma donation. We present the first case, to our knowledge, of lower extremity oedema as the only complication noted following plasma donation in an adolescent female without underlying risk factors. Laboratory evaluation was unremarkable with the exception of decreased total serum protein. Symptoms resolved with conservative management and avoidance of plasma donation. Our case highlights the importance of screening for all sources of income in adolescents to assess for health disparities, evaluate risk factors and provide appropriate guidance.

Surgical operations at Massachusetts General Hospital in 1846 and 1847: Early impact of the discovery of anaesthesia.

The introduction of anaesthesia on 16 October 1846 brought about tremendous changes in the discipline of surgery. We sought to determine whether the concept of painless surgery was accepted by practitioners and patients, and whether this led to an increase in frequency and variety of surgical operations performed. To study these changes, we analysed surgical records from Massachusetts General Hospital, Boston, Massachusetts (MGH) in the months surrounding the discovery of ether anaesthesia. Surgical records from MGH between 25 February 1846 and 14 March 1847 were examined, and the variables studied included number of operations, type of operations, patient demographics, complications and analgesics used, as well as comments made by surgeons. Immediately following the introduction of anaesthesia, MGH experienced a sizeable increase in the volume of surgical operations. This included a doubling in the percentage of female patients undergoing surgery. Orthopaedic procedures and amputations both increased in frequency, as did the number of surgeons operating. Several records indicated the presence of postoperative wound infection. Operations were still performed without anaesthesia. Following the introduction of ether anaesthesia in 1846, surgical volume increased, and more women underwent surgery. This suggests early acceptance of anaesthesia by patients and the medical profession. In an era prior to the introduction of antiseptic and aseptic techniques it is not surprising that wound infections were observed in several patients. We provide a glimpse of anaesthesia and surgery during the first few months after the first public demonstration of anaesthesia at MGH.

Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis.

High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by an immunosuppressive tumor microenvironment containing few tumor infiltrating lymphocytes (TILs) and an insensitivity to checkpoint inhibitor immunotherapies. Gains in the PTK2 gene encoding focal adhesion kinase (FAK) at Chr8 q24.3 occur in ∼70% of HGSOC tumors, and elevated FAK messenger RNA (mRNA) levels are associated with poor patient survival. Herein, we show that active FAK, phosphorylated at tyrosine-576 within catalytic domain, is significantly increased in late-stage HGSOC tumors. Active FAK costained with CD155, a checkpoint receptor ligand for TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains), in HGSOC tumors and a selective association between FAK and TIGIT checkpoint ligands were supported by patient transcriptomic database analysis. HGSOC tumors with high FAK expression were associated with low CD3 mRNA levels. Accordingly, late-stage tumors showed elevated active FAK staining and significantly lower levels of CD3+ TILs. Using the KMF (Kras, Myc, FAK) syngeneic ovarian tumor model containing spontaneous PTK2 (FAK) gene gains, the effects of tumor intrinsic genetic or oral small molecule FAK inhibitior (FAKi; VS-4718) were evaluated in vivo. Blocking FAK activity decreased tumor burden, suppressed ascites KMF-associated CD155 levels, and increased peritoneal TILs. The combination of FAKi with blocking TIGIT antibody (1B4) maintained elevated TIL levels and reduced TIGIT+ T regulatory cell levels, prolonged host survival, increased CXCL13 levels, and led to the formation of omental tertiary lymphoid structures. Collectively, our studies support FAK and TIGIT targeting as a rationale immunotherapy combination for HGSOC.

Long-Term Effects of Fatherhood on Morphology, Energetics, and Exercise Performance in California Mice (Peromyscus californicus).

In male mammals that provide care for their offspring, fatherhood can lead to changes in behavioral, morphological, and physiological traits, some of which might constitute trade-offs. However, relatively little is known about these changes, especially across multiple reproductive bouts, which are expected to magnify differences between fathers and nonreproductive males. We evaluated consequences of fatherhood in the monogamous, biparental California mouse (Peromsycus californicus) across seven consecutive reproductive bouts. We compared breeding adult males (housed with sham-ovariectomized females) with two control groups: nonbreeding males (housed with ovariectomized females treated with estrogen and progesterone to induce estrous behavior) and virgin males (housed with untreated ovariectomized females). At five time points (before pairing, early postpartum of the first litter, late postpartum of the second litter, early postpartum of the sixth litter, and late postpartum of the seventh litter or comparable time points for nonbreeding and virgin males), we measured males' body composition, hematocrit, predatory aggression, resting metabolic rate, maximal oxygen consumption (V˙O2 max⁡), grip strength, and sprint speed. We also weighed organs at the final time point. We predicted that fathers would have lower relative body fat and lower performance abilities compared with control groups and that these effects would become more pronounced with increasing parity. Contrary to predictions, breeding and control males differed in surprisingly few measures, and the number and magnitude of differences did not increase with parity. Thus, our expectations regarding trade-offs were not met. As reported in studies of single reproductive events, these results suggest that fatherhood has few costs in this species when housed under standard laboratory conditions, even across multiple reproductive bouts.

Effects of short- and long-term cold acclimation on morphology, physiology, and exercise performance of California mice (Peromyscus californicus): potential modulation by fatherhood.

California mice (Peromyscus californicus) differ from most other mammals in that they are biparental, genetically monogamous, and (compared with other Peromyscus) relatively large. We evaluated effects of cold acclimation on metabolic rate, exercise performance, and morphology of pair-housed male California mice, as well as modulation of these effects by fatherhood. In Experiment 1, virgin males housed at 5° or 10 °C for approximately 25 days were compared with virgins housed at standard vivarium temperature of 22 °C. Measures included resting metabolic rate (RMR), maximal oxygen consumption ([Formula: see text]max), grip strength, and sprint speed. In Experiment 2, virgin males housed at 22 °C were compared with three groups of males housed at 10 °C: virgins, breeding males (housed with a female and their pups), and non-breeding males (housed with an ovariectomized, estrogen- and progesterone-treated female) after long-term acclimation (mean 243 days). Measures in this experiment included basal metabolic rate (BMR), [Formula: see text]max, maximal thermogenic capacity ([Formula: see text]sum), and morphological traits. In Experiment 1, virgin males housed at 5° and 10 °C had higher RMR and [Formula: see text]max than those at 22 °C. In Experiment 2, 10 °C-acclimated groups had shorter bodies; increased body, fat, and lean masses; higher BMR and [Formula: see text]sum, and generally greater morphometric measures and organ masses than virgin males at 22 °C. Among the groups housed at 10 °C, breeding males had higher BMR and lower [Formula: see text]max than non-breeding and/or virgin males. Overall, we found that effects of fatherhood during cold acclimation were inconsistent, and that several aspects of cold acclimation differ substantially between California mice and other small mammals.

Intermittent Dieting: Theoretical Considerations for the Athlete.

Athletes utilise numerous strategies to reduce body weight or body fat prior to competition. The traditional approach requires continuous energy restriction (CER) for the entire weight loss phase (typically days to weeks). However, there is some suggestion that intermittent energy restriction (IER), which involves alternating periods of energy restriction with periods of greater energy intake (referred to as 'refeeds' or 'diet breaks') may result in superior weight loss outcomes than CER. This may be due to refeed periods causing transitory restoration of energy balance. Some studies indicate that intermittent periods of energy balance during energy restriction attenuate some of the adaptive responses that resist the continuation of weight and fat loss. While IER-like CER-is known to effectively reduce body fat in non-athletes, evidence for effectiveness of IER in athletic populations is lacking. This review provides theoretical considerations for successful body composition adjustment using IER, with discussion of how the limited existing evidence can be cautiously applied in athlete practice.

Effects of a physical and energetic challenge on male California mice (Peromyscus californicus): modulation by reproductive condition.

Reproduction strongly influences metabolism, morphology and behavior in female mammals. In species in which males provide parental care, reproduction might have similar effects on fathers. We examined effects of an environmental challenge on metabolically important physiological, morphological and behavioral measures, and determined whether these effects differed between reproductive and non-reproductive males in the biparental California mouse (Peromyscus californicus). Males were paired with an ovary-intact female, an ovariectomized female treated with estrogen and progesterone to induce estrus, or an untreated ovariectomized female. Within each group, half of the animals were housed under standard laboratory conditions and half in cages requiring them to climb wire towers to obtain food and water; these latter animals were also fasted for 24 h every third day. We predicted that few differences would be observed between fathers and non-reproductive males under standard conditions, but that fathers would be in poorer condition than non-reproductive males under challenging conditions. Body and fat mass showed a housing condition×reproductive group interaction: the challenge condition increased body and fat mass in both groups of non-reproductive males, but breeding males were unaffected. Males housed under the physical and energetic challenge had higher blood lipid content, lower maximal aerobic capacity and related traits (hematocrit and relative triceps surae mass), increased pain sensitivity and increased number of fecal boli excreted during tail-suspension tests (a measure of anxiety), compared with controls. Thus, our physical and energetic challenge paradigm altered metabolism, morphology and behavior, but these effects were largely unaffected by reproductive condition.

Periodontitis: a global disease and the primary care provider's role.

Individuals who regularly visit a primary care provider (PCP) may not see a dentist, creating opportunities for PCPs to improve oral health. However, a lack of expertise among PCPs may limit their impact to improve public oral health. Using a non-systematic literature review, this article summarises the relevant literature about periodontitis. Periodontitis affects 10% to -15% of the world's population. Caused by bacterial inflammation in gingival pockets, periodontal disease can destroy tissues surrounding the teeth. Factors linked to periodontal disease include diabetes, atherosclerosis and smoking. Good oral hygiene is important for both prevention and treatment. Mechanical removal of gingival irritants by scaling and root planing combined with adjunctive antimicrobial therapy are first-line treatment options. Surgery is indicated when healthy levels of gingival tissue are not attained from first-line treatments. By understanding the fundamentals of periodontitis the primary care provider can educate patients, promote healthy oral health behaviours and appropriately refer patients with signs and symptoms of periodontal disease.

Paternal Care in Biparental Rodents: Intra- and Inter-individual Variation.

Parental care by fathers, although rare among mmmals, can be essential for the survival and normal development of offspring in biparental species. A growing body of research on biparental rodents has identified several developmental and experiential influences on paternal responsiveness. Some of these factors, such as pubertal maturation, interactions with pups, and cues from a pregnant mate, contribute to pronounced changes in paternal responsiveness across the course of the lifetime in individual males. Others, particularly intrauterine position during gestation and parental care received during postnatal development, can have long-term effects on paternal behavior and contribute to stable differences among individuals within a species. Focusing on five well-studied, biparental rodent species, we review the developmental and experiential factors that have been shown to influence paternal responsiveness, and consider their roles in generating both intra- and inter-individual variation. We also review hormones and neuropeptides that have been shown to modulate paternal care and discuss their potential contributions to behavioral differences within and between males. Finally, we discuss the possibility that vasopressinergic and possibly oxytocinergic signaling within the brain, modulated by gonadal steroid hormones, may represent the "final common pathway" mediating effects of developmental and experiential variables on intra- and inter-individual variation in paternal care.

Metabolic and affective consequences of fatherhood in male California mice.

Physiological and affective condition can be modulated by the social environment and parental state in mammals. However, in species in which males assist with rearing offspring, the metabolic and affective effects of pair bonding and fatherhood on males have rarely been explored. In this study we tested the hypothesis that fathers, like mothers, experience energetic costs as well as behavioral and affective changes (e.g., depression, anxiety) associated with parenthood. We tested this hypothesis in the monogamous, biparental California mouse (Peromyscus californicus). Food intake, blood glucose and lipid levels, blood insulin and leptin levels, body composition, pain sensitivity, and depression-like behavior were compared in males from three reproductive groups: virgin males (VM, housed with another male), non-breeding males (NB, housed with a tubally ligated female), and breeding males (BM, housed with a female and their first litter). We found statistically significant (P<0.007, when modified for Adaptive False Discovery Rate) or nominally significant (0.007

Interventional Drug-Induced Sleep Endoscopy: A Novel Technique to Guide Surgical Planning for Obstructive Sleep Apnea.

STUDY OBJECTIVE: One of the challenges of surgery for obstructive sleep apnea (OSA) is identifying the correct surgical site for each patient. The objective of this study was to use drug-induced sleep endoscopy (DISE) and nasopharyngeal tube (NPT) placement to determine the effect of eliminating palatal collapse on the obstruction seen on other segments of the upper airway. METHODS: Forty-one OSA patients were enrolled in this prospective study. All patients had a polysomnogram followed by DISE. DISE findings were recorded and compared with and without placement of a NPT. Obstruction was graded with a scale that incorporates location, severity, and interval of obstruction. RESULTS: Most patients (83%) demonstrated multilevel obstruction on initial DISE. With the nasopharyngeal airway in place, many patients with multilevel obstruction had at least a partial improvement (74%) and some a complete resolution (35%) of collapse (p < 0.05). Reduction in collapse was observed at the lateral walls (86%), epiglottis (55%), and tongue base (50%). NPT placement did not significantly alter upper airway morphology of patients with incomplete palatal obstruction or mild OSA. CONCLUSIONS: To our knowledge, this is the first study to evaluate the effect of soft palatal stenting on downstream pharyngeal obstruction during DISE. Our study provides evidence that reducing soft palatal collapse can reduce negative pharyngeal pressure and thereby alleviate other sites of upper airway obstruction. Taken together, these findings provide a means to identify appropriate candidates for isolated palatal surgery and better direct a minimally invasive approach to the surgical management of OSA.

Cholesteryl Ester Transfer Protein Inhibitors: Trials and Tribulations.

The cholesteryl ester transfer protein (CETP) is a plasma protein that plays an important role in the transfer of lipids between plasma lipoproteins. The CETP inhibitors have been widely studied as a pharmacologic therapy to target plasma cholesterol in order to reduce the risk of atherosclerotic cardiovascular disease . Using CETP inhibitors as cholesterol modifiers was based on the genetic research that found correlations between CETP activity and cholesterol levels. Although CETP inhibitors are successful at altering targeted cholesterol markers, recent phase 3 outcome trials have shown limited benefit on cardiovascular outcomes when combined with the current standard of care. We discuss the science of CETP inhibition, compare the CETP inhibitors developed (torcetrapib, evacetrapib, dalcetrapib, and anacetrapib), the findings from the CETP inhibitor trials, and the future outlook for CETP inhibitors in cholesterol modification.

Consequences of Fatherhood in the Biparental California Mouse (Peromyscus californicus): Locomotor Performance, Metabolic Rate, and Organ Masses.

Although effects of motherhood on mothers have been well documented in mammals, the effects of fatherhood on fathers are not well known. We evaluated effects of being a father on key metabolic and performance measures in the California mouse, Peromyscus californicus. California mice are genetically monogamous in the wild, and fathers show similar parental behavior to mothers, with the exception of lactation. To investigate the impact of fatherhood on fathers, focal males were paired with an intact female (breeding males), a tubally ligated female (nonbreeding males), or another male (virgins). Starting 3-5 d after the birth of each breeding pair's first litter, males were tested for locomotor performance (maximum sprint speed, treadmill endurance), basal metabolic rate (BMR), and maximum oxygen consumption ([Formula: see text]). At the end of the 11-d test period, mice were euthanized, hematocrit was determined, and organs were weighed. Speed, endurance, and [Formula: see text] were significantly repeatable between two replicate measurement days but did not differ among groups, nor did BMR. Breeding males had significantly larger hind limb muscles than did nonbreeding males, whereas virgin males had heavier subcutaneous fat pads than did nonbreeding and breeding males. Several correlations were observed at the level of individual variation (residuals from ANCOVA models), including positive correlations for endurance with [Formula: see text], [Formula: see text] with testes mass, and some of the digestion-related organs with each other. These results indicate that fatherhood may not have pronounced performance, metabolic, or morphological effects on fathers, at least under standard laboratory conditions and across a single breeding cycle.

Effects of nasal surgery on the upper airway: a drug-induced sleep endoscopy study.

OBJECTIVES/HYPOTHESIS: To evaluate the impact of nasal surgery on the oropharyngeal and hypopharyngeal anatomy of patients with obstructive sleep apnea (OSA) by comparing drug-induced sleep endoscopy (DISE) data prior to and following nasal surgery. STUDY DESIGN: Retrospective review of medical records and DISE video recordings. METHODS: Twenty-four patients with OSA were identified who underwent nasal surgery for symptomatic nasal obstruction. Clinic charts and DISE video recordings were reviewed. Preoperative and postoperative DISE recordings were compared to determine whether nasal surgery affected the level, degree, and sustainability of upper airway obstruction. RESULTS: Overall, the pattern of upper airway obstruction did not change significantly following nasal surgery (P > .05). Almost all patients demonstrated residual obstruction by postoperative DISE (96%), with no change in plans for surgical management of oropharyngeal and hypopharyngeal collapse (83%). Partial improvement in palatal collapse was present in a subset of patients without tongue base obstruction (P < .05). Postoperative apnea-hypopnea index decreased from a mean of 23.6 to 20.4 events/hr, but this change was not significant (P > .05). CONCLUSIONS: For most patients with OSA, surgical repair of nasal obstruction does not significantly improve oropharyngeal or hypopharyngeal collapse as seen on DISE. However, mild improvement in palatal collapse is seen in a subset of patients without tongue base obstruction. This study reveals that if DISE is being utilized to direct surgical management of OSA, it does not need to be repeated for most patients after nasal surgery.