To acquire the ability to fertilize, spermatozoa undergo complex, but at present poorly understood, activation processes. The intracellular rise of cAMP produced by the bicarbonate-dependent soluble ...adenylyl cyclase (sAC) has been suggested to play a central role in initiating the cascade of the events that culminates in spermatozoa maturation. Here, we show that targeted disruption of the sAC gene does not affect spermatogenesis but dramatically impairs sperm motility, leading to male sterility. sAC mutant spermatozoa are characterized by a total loss of forward motility and are unable to fertilize oocytes in vitro. Interestingly, motility in sAC mutant spermatozoa can be restored on cAMP loading, indicating that the motility defect observed is not caused by a structural defect. We, therefore, conclude that sAC plays an essential and nonredundant role in the activation of the signaling cascade controlling motility and, therefore, in fertility. The crucial role of sAC in fertility and the absence of any other obvious pathological abnormalities in sAC-deficient mice may provide a rationale for developing inhibitors that can be applied as a human male contraceptive.
Low serum 25 hydroxyvitamin D3 (vitamin D3) is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in obesity and type II diabetes mellitus ...(TIIDM). Vitamin D3 insufficiency has been linked to obesity, whether obesity is assessed by body mass index (BMI) or waist circumference (waist). Central obesity, using waist as the surrogate, is associated with the metabolic syndrome (MetSyn), insulin resistance, TIIDM and atherosclerotic cardiovascular disease (CVD). We tested how vitamin D3 was related to measures of fat mass, MetSyn markers, haemoglobin A1c (HbA1c) and MetSyn in a cross-sectional sample of 250 overweight and obese adults of different ethnicities. There were modest inverse associations of vitamin D3 with body weight (weight) (r = -0.21, p = 0.0009), BMI (r = -0.18, p = 0.005), waist (r = -0.14, p = 0.03), but not body fat % (r = -0.08, p = 0.24), and HbA1c (r = -0.16, p = 0.01). Multivariable regression carried out separately for BMI and waist showed a decrease of 0.74 nmol/L (p = 0.002) in vitamin D3 per 1 kg/m2 increase in BMI and a decrease of 0.29 nmol/L (p = 0.01) per 1 cm increase in waist, with each explaining approximately 3% of the variation in vitamin D3 over and above gender, age, ethnicity and season. The similar relationships of BMI and waist with vitamin D3 may have been due to associations between BMI and waist, or coincidental, where different mechanisms relating hypovitaminosis D3 to obesity occur concurrently. Previously reviewed mechanisms include that 1) low vitamin D3, may impair insulin action, glucose metabolism and various other metabolic processes in adipose and lean tissue 2) fat soluble-vitamin D3 is sequestered in the large adipose compartment, and low in serum, 3) obese people may be sensitive about their body shape, minimising their skin exposure to view and sunlight (not tested). We showed evidence for the first theory but no evidence to support the second. In the current study, serum vitamin D3 was inversely related to weight, BMI and markers of TIIDM (large waist, raised HbA1c) but not to adipose mass nor to MetSyn per se.
One of the most important questions remaining in matters of critical illness in the year 2019 is arguably how to address the diverse neuropsychiatric complications of critical illness.
The ICD-11 and ...DSM-5, two of the world's leading classification systems, disagree regarding important aspects of delirium; moreover, they do not mention critical illness and its neuropsychiatric complications at all.
It would have been desirable for the committees revising the DSM-IV-TR and ICD-10 to have joined forces in order to generate classification systems that complement each other and, moreover, that address the "The Neuro-Psychiatry of Critical Illness".
Lost in another language: a case report Salamah, Husam K Z; Mortier, Eva; Wassenberg, Renske ...
Journal of medical case reports,
01/2022, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In foreign language syndrome, patients switch from their native language and fixate for a period of time on a second language. There have been few reported cases. The language switch typically occurs ...postoperatively and spontaneously resolves after a short period of time. The primary cause of this switching remains unclear. There is speculation about the involvement of anesthesia, but its specific influence remains unclear.
A 17-year-old Dutch Caucasian male lost the ability to understand and speak Dutch for 24 hours after an orthopedic surgery, combined with a brief confused state including disorientation of place and the inability to recognize his parents. During the period, he communicated in English, which he had learned during school classes but had never spoken outside of school. Further follow-up, including neuropsychological examination, revealed no indication of cognitive impairment.
The exact pathophysiology of foreign language syndrome remains unclear, most specifically whether it is a syndrome of its own or a phenotype of emergence delirium. There is still much to be learned, and further research is needed.
Background
Laparoscopic cholecystectomy is one of the most common surgical procedures in Europe (and the world) and has become the standard procedure for the management of symptomatic cholelithiasis ...or acute cholecystitis in patients without specific contraindications. Bile duct injuries (BDI) are rare but serious complications that can occur during a laparoscopic cholecystectomy. Prevention and management of BDI has given rise to a host of publications but very few recommendations, especially in Europe.
Methods
A systematic research of the literature was performed. An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. Statements and recommendations were drafted after a consensus development conference in May 2011, followed by presentation and discussion at the annual congress of the EAES held in Torino in June 2011. Finally, full guidelines were consented and adopted by the expert panel via e-mail and web conference.
Results
A total of 1,765 publications were identified through the systematic literature search and additional submission by panellists; 671 publications were selected as potentially relevant. Only 46 publications fulfilled minimal methodological criteria to support Clinical Practice Guidelines recommendations. Because the level of evidence was low for most of the studies, most statements or recommendations had to be based on consensus of opinion among the panel members. A total of 15 statements and recommendations were developed covering the following topics: classification of injuries, epidemiology, prevention, diagnosis, and management of BDI.
Conclusions
Because BDI is a rare event, it is difficult to generate evidence for prevention, diagnosis, or the management of BDI from clinical studies. Nevertheless, the panel has formulated recommendations. Due to the currently limited evidence, a European registry should be considered to collect and analyze more valid data on BDI upon which recommendations can be based.
Therapeutic Immunization against Glioblastoma Schijns, Virgil E J C; Pretto, Chrystel; Strik, Anna M ...
International journal of molecular sciences,
08/2018, Letnik:
19, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually ...surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient's immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.
Malignant gliomas, the most common malignant primary brain tumors, have a deleterious clinical prognosis of approximately 12 months in unselected series. The resistance against antineoplastic therapy ...is apparently not only associated with a high proliferative potential, marked antiapoptotic resistance and high migratory capacity. Effective mechanisms to escape the immune response of the organism and an intense neoangiogenesis also contribute to the aggressive growth of these neoplasms. In addition to a number of molecular mechanisms, the group of glycohydrate-binding galectins seems to contribute to the aggressive growth of malignant gliomas. Galectin-1, -3, -4 and -8 have been shown to be overexpressed in malignant gliomas. Galectin-1 is known to be involved in glioma cell migration and possibly also in proliferation. In this review, various aspects of glioma biology and their therapeutic relevance is discussed. The role of galectins in apoptosis-resistance, immune response and angiogenesis is discussed and explained why these molecules are interesting targets of glioma therapy.
Purpose
Laparoscopic inguinal hernia repair (IHR) may lead to early postoperative pain. Therefore, opioid and non-opioid analgesic agents are often administered in the post-anesthesia care unit ...(PACU). To reduce the postoperative cumulative need of analgesic medication, as well as to accelerate the physical recovery time, the transversus abdominis plane (TAP) block has recently been studied. The TAP block is a regional anesthesia technique. Even though there is evidence about the efficacy of the block used in procedure such as an open inguinal hernia repair, the evidence regarding its use for the TAPP (transabdominal preperitoneal) technique remains low. We aim to provide more sufficient evidence regarding this topic.
Methods
A monocentric retrospective observational study investigating the effect of the TAP block prior to primary IHR in TAPP technique was conducted. The data of 838 patients who were operated on using this technique from June 2007 to February 2019 were observed. 72 patients were excluded because of insufficient information regarding their analgesic medication protocol. The patients’ data were taken from their files.
Results
The patients in the TAP block group (
n
= 364) did not differ statistically significantly compared to the control group (
n
= 402) in terms of gender, BMI and age. Individuals of the TAP block group experienced less postoperative pain in the PACU (
p
< 0.001) and received less analgesic medication (morphine, oxycodone, piritramide, acetaminophen;
p
< 0.001).
Conclusion
We assume that the TAP block is a sufficient approach to reduce postoperative pain and analgesic medication administration for IHR in TAPP technique.
Abstract High-fat diets are associated with obesity, and the weak satiety response elicited in response to dietary lipids is likely to play a role. Preliminary evidence from studies of medium (MCT) ...and long chain triglycerides (LCT) supports greater appetite suppression on high-MCT diets, possibly a consequence of direct portal access, more rapid oxidation and muted lipaemia. No data is as yet available on high-SCT diets which also have direct hepatic access. In this study SCT- (dairy fats), MCT- (coconut oil) and LCT-enriched (beef tallow) test breakfasts (3.3 MJ) containing 52 g lipid (58 en% fat) were investigated in a randomized, cross-over study in 18 lean men. All participants were required to complete the 3 study days in randomised order. Participants rated appetite sensations using visual analogue scales (VAS), and energy intake (EI) was measured by covert weighing of an ad libitum lunch meal 3.5 h postprandially. Blood samples were collected by venous cannulation. There were no detectable differences between breakfasts in perceived pleasantness, visual appearance, smell, taste, aftertaste and palatability ( P > 0.05). There was no significant effect of fatty acid chain length on ratings of hunger, fullness, satisfaction or current thoughts of food, nor did energy (mean, sem: SCT: 4406, 366 kJ; MCT: 4422, 306 kJ; LCT: 4490, 324 kJ; P > 0.05) or macronutrient intake at lunch differ between diets. The maximum difference in EI between diets was less than 2%. Postprandial lipaemia also did not differ significantly. We conclude that there was no evidence that fatty acid chain length has an effect on measures of appetite and food intake when assessed following a single high-fat test meal in lean participants.
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