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Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved. Here, we investigated the role of these buried CLs in AAC/ANT using a combination of biochemical approaches, native mass spectrometry, and molecular dynamics simulations. We introduced negatively charged mutations into each CL-binding site of yeast Aac2 and established experimentally that the mutations disrupted the CL interactions. While all mutations destabilized Aac2 tertiary structure, transport activity was impaired in a binding site-specific manner. Additionally, we determined that a disease-associated missense mutation in one CL-binding site in human ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions., (© 2024. The Author(s).)

Resistance to available antibiotics poses a growing challenge to modern medicine, as this often disallows infections to be controlled. This problem can only be alleviated by the development of new drugs. Nisin, a natural lantibiotic with broad antimicrobial activity, has shown promise as a potential candidate for combating antibiotic-resistant bacteria. However, nisin is poorly soluble and barely stable at physiological pH, which despite attempts to address these issues through mutant design has restricted its use as an antibacterial drug. Therefore, gaining a deeper understanding of the antimicrobial effectiveness, which relies in part on its ability to form pores, is crucial for finding innovative ways to manage infections caused by resistant bacteria. Using large-scale molecular dynamics simulations, we find that the bacterial membrane-specific lipid II increases the stability of pores formed by nisin and that the interplay of nisin and lipid II reduces the overall integrity of bacterial membranes by changing the local thickness and viscosity.

Overexpression of serum amyloid A (SAA) can lead to a form of amyloidosis where the fibrils are made of SAA fragments, most often SAA 1-76 . Using Replica Exchange with Tunneling, we study the conversion of a SAA 1-76 chain between the folded conformation and a fibril conformation. We find that the basins in the free energy landscape corresponding to the two motifs are separated by barriers of only about 2-3 k B T . Crucial for the assembly into the fibril structure is the salt bridge 26E-34K that provides a scaffold for forming the fibril conformation., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Itch, inflammation, and atopic dermatitis are associated with activation of PAR2. Affecting PAR2 activity presents a number of challenges. Here, a cell-penetrating peptide, termed a pepducin, circumvents these challenges by preventing the receptor from coupling to G proteins. The pepducin modulates several models of itch, inflammation, and atopic dermatitis., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Approximately 25% of patients require reoperation within 15 yrs of a Ross procedure. Increasing experience with valve-sparing root replacement (VSRR) has led some surgeons to spare the autograft valve. Here, we demonstrate that all valves can be surgically repaired or replaced safely during autograft VSRR. As more patients are considered for this operation, coexistent mitral, tricuspid, and pulmonic valve dysfunction should not preclude salvage of the autograft valve, nor should autograft leaflet prolapse.

We describe the surgical technique for mitral and tricuspid valve repair using a minimally invasive approach in a patient with situs inversus totalis., (© 2016 Wiley Periodicals, Inc.)

Objective: This article presents an updated review of the literature of Munchausen Syndrome by Proxy (Factitious Disorder by Proxy, MBP)., Method: Four hundred fifty-one cases of MBP were analyzed from 154 medical and psychosocial journal articles., Results: Typical victims may be either males or females, usually 4 years of age or under. Victims averaged 21.8 months from onset of symptoms to diagnosis. Six percent of victims were dead, and 7.3% were judged to have suffered long-term or permanent injury. Twenty-five percent of victims' known siblings are dead, and 61.3% of siblings had illnesses similar to those of the victim or which raised suspicions of MBP. Mothers were perpetrators in 76.5% of cases, but as knowledge of MBP grows a wider range of perpetrators is identified. In a small number of cases, MBP was found to co-exist with secondary gain or other inflicted injury., Conclusion: Although published cases form a non-random sample, they add to knowledge about MBP and validate claims that it occurs. More knowledge about non-medical aspects of MBP, and more pooling of data, is desirable.

Pediatricians and family practitioners were asked how accurately parents report young children's symptoms. They believe 5% conceal/fail to report, 8% minimize, 80% report accurately, 10% exaggerate, and 1% falsely report/induce symptoms. They report fewer puzzling cases in their own practices than these estimates would suggest. Health professionals should know the warning signs of Munchausen syndrome by proxy.

Sudden Infant Death Syndrome may exhibit chaotic behavior because it fits common characteristics of chaotic systems including unpredictability, sensitivity to initial conditions, dependence on parameters, and coupling. Chaos theory suggests that preventive efforts should be added to those directed toward a 'cure'.

In summary, event recording is a cost-effective means of obtaining objective evidence about a baby's cardiorespiratory patterns at home. It is particularly useful in joint decisionmaking at the time of discharge if parents (or clinicians) remain anxious about the status of a child. Event recording is also indicated in the followup of families where there are multiple or questionable reports of serious events at home. In such instances it may clarify whether symptoms are worthy of concern, and may play a role in problem resolution. Monitors are now available that continuously record events and compliance (for example, the E-link system produced by Corometrics Medical Systems, Inc., Wallingford, Connecticut). Such monitors will reduce parental anxiety, facilitate more prompt diagnosis and treatment of genuine disease states, and make possible the further exploration of relationships between parental anxiety and symptom reporting. Although there are technical trade-offs with such monitors (for example, shorter battery life) and higher personnel costs associated with the transcription of recordings, the total length of monitoring and the need for rehospitalization or evaluation of symptoms may be decreased, thus making such monitors cost effective.

The authors sent questionnaires to 127 apnea monitoring programs asking whether they had treated patients whose apnea appeared to have been induced by a parent (Munchausen syndrome by proxy-apnea, or MBPA). Fifty-one programs (40%) reported 54 cases of this kind from among their 20,090 monitored patients (0.27%). The authors obtained further information on 32 of these patients, 83% of whom presented with infantile apnea before the third month of life. Although medical problems were documented, including apnea, the clinical condition of these infants was inconsistent with the multiple life-threatening episodes typically reported by parents. Twenty-one of the infants reportedly received cardiopulmonary resuscitation at home, 15 had ambulance calls to the home, and 24 were rehospitalized. Child Protective Service agencies were consulted for 12 patients, 5 of whom were placed in foster homes. Three index infants and five siblings are known to be dead, and one additional infant is severely brain damaged from abuse.

Home equipment for cardiorespiratory monitoring now makes it possible for parents to manage more effectively the risks of apnea, or prolonged breathing pauses, in infants. This article examines the features of a social work program that provides parents of apneic infants with education and support. It also demonstrates the important contribution of social work to monitoring.

The pathophysiology of "near miss" or "aborted" sudden infant death syndrome (better termed "emergency apnea") is unclear. Emotionally, however, such episodes are significantly stressful for parents. We administered a questionnaire to 50 families who had experienced emergency apnea at home. Sixty percent ranked the experience as one of the most difficult in their lives; 56% believed that the infant's death was averted only because they intervened. The psychodynamics are similar to those seen in families who have lost an infant to sudden infant death syndrome, and they are consistent with post-traumatic stress disorder. The affected infants may be regarded as "vulnerable children." Many parents believed that their lives were permanently changed. Home apnea monitoring equipment and support from the family physician and monitoring program are important in reducing the stress associated with apneic emergencies.

Munchausen syndrome by proxy (MBP) is the deliberate induction or reporting of physical symptoms in a child. It is a form of child abuse that can result in death, iatrogenic disease, or the masking of a genuine illness. MBP is suggested by symptoms that do not follow the usual course of illness, particularly if the symptoms only occur in the presence of the same person. MBP may occur when caretakers (usually mothers) perceive that being the parent of a sick child will solve personal conflicts and be socially rewarded, or if life experiences have demonstrated that the price of love is physical illness. When MBP is suspected, the health care team needs to take aggressive action to confirm or disprove it and to protect the child. A social worker confronted with possible MBP must manage a difficult situation that often involves painful team issues as well as confusion over the nature of reality.

By February 1988, 1,000 Hawaii infants had been prescribed cardiorespiratory monitors for use at home. By 1986, 12.3/1000 live births were being monitored, principally for apnea related to prematurity but also following Apparent Life Threatening Episodes, (ALTE) as subsequent siblings of Sudden Infant Death Syndrome (SIDS) victims, and for an increasing variety of other conditions. Less than 3% of families used the monitor less than 1 week; 30% discontinued sooner than the program recommended. Twenty-seven percent of the monitored infants were judged to have experienced real apnea or bradycardia while on their monitors. Seventeen of the patients are known to be dead, with 2 of these deaths occurring while the symptomatic patient was not monitored. Parents responding to a quality assurance questionnaire were highly enthusiastic about monitoring and felt it was a source of reassurance rather than a stressor. Major problems encountered by monitoring families were related to equipment performance.

Health care social workers face significant problems in controlling and managing time. Among the causes are increased demands for service, economy measures in health care, and the concurrent responsibility which social workers often have for both ongoing case management and crisis coverage. Individuals and social work departments can increase productivity through streamlining case management, increasing use of available resources, and generating new resources. With planning and preparation, many emergencies can be moved into the expected work flow. The social work profession needs to address time management problems and expectations in a more realistic and systematic way.

The concerned worker needs to know how children perceive the hospital. The institution, the illness, and the procedures evoke specific reactions in children. They fantasize about all of these, and question whether the hospital will help them. Through good communication, consideration, and sound information, it is possible to maximize the positive aspects of a hospitalization experience.

Why should a social worker be on the team of a neonatal intensive-care nursery? Helping parents cope with the crises that arise with high-risk births is only one important reason. Ameliorating staff stress is another. Also, by following up the high-risk babies, the social worker has an opportunity to play a preventive role.

Kinins and angiotensins affect renal and intestinal function and are rapidly converted and/or inactivated in the renal proximal tubule and intestinal tract by converting enzyme, kininases and angiotensinases of the brush border. Converting enzyme accounts for only 40% of intestinal kininases activity. Thus inhibition of converting enzyme by captopril, while completely inhibiting intestinal angiotensin II generation, may only partially inhibit kinin inactivation. In the kidney, however, converting enzyme accounts for the majority of renal kininase activity. Thus the effect of captopril on inhibition of renal angiotensin II formation and kinin inactivation may be similar. Using monospecific antibody to purified converting enzyme and techniques of rocket and fused-rocket immunoelectrophoresis, renal and intestinal converting enzyme can be detected, quantitated and partially characterized. The immunologic localization of renal and intestinal converting enzyme is identical to its enzymatic localization. Immunoelectrophoretic analysis of membrane-bound peptidases is a valuable approach to investigating membrane metabolism of vasoactive peptides.