Efficacy of Osteopathic Manipulative Treatment for Pain Reduction in Patients With Patellofemoral Pain Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Patellofemoral pain syndrome (PFPS) is among the most common causes of musculoskeletal pain in the United States. It is defined as retropatellar or peripatellar pain that is reproduced with functional activities that load the patellofemoral joint in a flexed position, such as stair climbing or squatting. While it presents in both adolescents and adults, it is commonly found in physically active individuals, such as athletes and military recruits. Exploring the role of osteopathic manipulative treatment (OMT) in PFPS is of particular interest given the absence of a definitive treatment and the poor long-term prognosis associated with PFPS. This meta-analysis includes three studies exploring the use of OMT to reduce pain in patients suffering from PFPS and exploring the efficacy of OMT as a primary intervention. In these studies, pain assessments, pre-treatment, and post-treatment follow-up of at least 30 days were performed using a 10-cm visual analog scale (VAS). The mean difference in pain between OMT and no treatment (NT) groups using the random effects model was -3.95 (-6.39; -1.50) with a p<0.01, suggesting OMT resulted in significant knee pain reduction in those with PFPS. A measure of heterogeneity, known as I2, was found to be high at 97%, which suggests caution should be taken when interpreting the overall results. Given the lack of definitive treatment and the poor long-term prognosis for PFPS, the authors suggest OMT provides an effective option for pain relief in patients with PFPS. Further research is needed to provide results that may be more clinically applicable or valuably interpreted.

The Value of Interdisciplinary Collaboration in Lateral Medullary Syndrome Rehabilitation: A Case Report.

Wallenberg's syndrome, also known as lateral medullary syndrome (LMS), is a neurological condition resulting from damage to the lateral portion of the medulla oblongata. We present a case of a 64-year-old man with Wallenberg's syndrome who presented for acute rehabilitation after sustaining a cerebrovascular accident (CVA). As seen in our patient, common symptoms of LMS include difficulty swallowing, hoarseness, ipsilateral weakness, and ipsilateral loss of sensation or numbness. Although the prognosis following infarction is often good, dysfunction in swallowing is one of the key deficits that have a long-term impact on patient quality of life. We aim to emphasize the significance of the interdisciplinary approach to achieving favorable health outcomes in patients with LMS.

Conservative Management of Postoperative Urinary Leak and Intra-Abdominal Abscess.

Ureteral injury is a rare occurrence in medical practice. Most cases encountered stem from blunt trauma or are iatrogenic, occurring during open abdominal or pelvic surgery and laparoscopic procedures. Prompt diagnosis of ureteral injury allows clinicians to avoid complications including ureteral strictures, abscess, renal failure, sepsis, and loss of the ipsilateral kidney. Treatment depends on whether the ureteral injury was discovered intraoperatively or if it was a delayed diagnosis. Several procedures can be used, including ureteroureterostomy, ureteroileal interposition, and nephrectomy. Stenting can also be a viable option as it can reestablish urinary drainage. Herein, we present the case of a 43-year-old male who presented with complaints of progressive abdominal pain that was subsequently diagnosed as a left ureteral injury and how the use of a ureteral stent allowed him to have a full recovery with optimized normal ureteral function.

Managing Chronic Regional Pain Syndrome: The Potential Impact of the Food and Drug Omnibus Reform Act.

Complex regional pain syndrome (CRPS) is a neurological disorder characterized by persistent limb symptoms. With there being no definitive tests, diagnosis can be challenging. The Budapest criteria are the standard for diagnosis. The underlying mechanisms of CRPS involve changes in skin innervation, sensitization of the nervous system, inflammatory cytokines, and genetic and psychological factors. Treatment typically involves a multidisciplinary approach. We present a case of a 71-year-old male with CRPS involving the right upper extremity and a complex history of management including physical therapy, oxycodone, muscle relaxers, non-steroidal anti-inflammatory drugs, and multiple stellate ganglion blocks. The patient manages his pain with off-label medications, including methadone, duloxetine, and pregabalin. In the United States, the management of chronic pain may be affected by potential usage restrictions imposed by the Food and Drug Omnibus Reform Act (FDORA). Under this new act, physicians may face limitations in prescribing off-label medications for specific diagnoses. We aim to highlight the need for prioritizing patient care and individualized treatment in healthcare policy decision-making.

Long-Term Retained Lippes Loop Intrauterine Device Causes Vesicouterine Fistula.

This case report discusses a 77-year-old female patient who presented to an outpatient clinic with urinary symptoms and recurrent UTIs. Imaging revealed a foreign body, which was later confirmed as a retained intrauterine device (IUD) that had caused a vesicouterine fistula (VUF). The patient had a medical history of cervical cancer treated with radiation therapy, during which her IUD's string could not be located, leading to the decision to proceed with radiation therapy without removing the IUD. The patient opted to manage her condition medically rather than undergo surgical removal due to concerns about worsening the vesicouterine fistula. This case highlights the potential risks and complications of retained IUDs, and the importance of careful consideration and communication among clinical teams and patients when managing these situations.

Academy of Breastfeeding Medicine Clinical Protocol #36: The Mastitis Spectrum, Revised 2022.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. The Academy of Breastfeeding Medicine recognizes that not all lactating individuals identify as women. Using gender-inclusive language, however, is not possible in all languages and all countries and for all readers. The position of the Academy of Breastfeeding Medicine (https://doi.org/10.1089/bfm.2021.29188.abm) is to interpret clinical protocols within the framework of inclusivity of all breastfeeding, chestfeeding, and human milk-feeding individuals.

Prophylactic nipple-sparing mastectomy in young previvors: Examining decision-making, reconstructive outcomes, and patient satisfaction in BRCA+ patients under 30.

Bilateral prophylactic mastectomies (BPM) in young previvors with high-risk mutations are rising; however, little data on management, therapy timing, and outcomes exist. BRCA+ patients under 30 undergoing BPM from 2006 to 2018 were reviewed. Twenty-two patients aged 23-29 underwent mastectomy 4.2 years after genetic diagnosis. Twelve patients completed surveys, most often citing personal decisions (50%) for undergoing mastectomy and plastic surgeons' recommendations (83.3%) for reconstruction. About 73% of patients completely understood risks/benefits of mastectomy and 63.6% of reconstruction. Patients reported high BREAST-Q Satisfaction and Well-Being scores. Continued educational resource development will optimize shared decision-making in the reconstructive process.

EZH1 is an antipsychotic-sensitive epigenetic modulator of social and motivational behavior that is dysregulated in schizophrenia.

BACKGROUND: With the capacity to modulate gene networks in an environmentally-sensitive manner, the role of epigenetic systems in mental disorders has come under intense investigation. Dysregulation of epigenetic effectors, including microRNAs and histone-modifying enzymes, may better explain the role of environmental risk factors and the observed heritability rate that cannot be fully attributed to known genetic risk alleles. Here, we aimed to identify novel epigenetic targets of the schizophrenia-associated microRNA 132 (miR-132). METHODS: Histone modifications were quantified by immunodetection in response to viral-mediated overexpression of miR-132 while a luminescent reporter system was used to validate targets of miR-132 in vitro. Genome-wide profiling, quantitative PCR and NanoSting were used to quantify gene expression in post-mortem human brains, neuronal cultures and prefrontal cortex (PFC) of mice chronically exposed to antipsychotics. Following viral-mediated depletion of Enhancer of Zeste 1 (EZH1) in the murine PFC, behaviors including sociability and motivation were assessed using a 3-chambered apparatus and forced-swim test, respectively. RESULTS: Overexpression of miR-132 decreased global histone 3 lysine 27 tri-methylation (H3K27me3), a repressive epigenetic mark. Moreover, the polycomb-associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated in the PFC of schizophrenics. Unlike its homolog EZH2, expression of EZH1 in the murine PFC decreased following chronic exposure to antipsychotics. Viral-mediated depletion of EZH1 in the mouse PFC attenuated sociability, enhanced motivational behaviors, and affected gene expression pathways related to neurotransmission and behavioral phenotypes. CONCLUSIONS: EZH1 is dysregulated in schizophrenia, sensitive to antipsychotic medications, and a brain-enriched miR-132 target that controls neurobehavioral phenotypes.

Nicotinic modulation of descending pain control circuitry.

Along with the well-known rewarding effects, activation of nicotinic acetylcholine receptors (nAChRs) can also relieve pain, and some nicotinic agonists have analgesic efficacy similar to opioids. A major target of analgesic drugs is the descending pain modulatory pathway, including the ventrolateral periaqueductal gray (vlPAG) and the rostral ventromedial medulla (RVM). Although activating nAChRs within this circuitry can be analgesic, little is known about the subunit composition and cellular effects of these receptors, particularly within the vlPAG. Using electrophysiology in brain slices from adult male rats, we examined nAChR effects on vlPAG neurons that project to the RVM. We found that 63% of PAG-RVM projection neurons expressed functional nAChRs, which were exclusively of the α7-subtype. Interestingly, the neurons that express α7 nAChRs were largely nonoverlapping with those expressing µ-opioid receptors (MOR). As nAChRs are excitatory and MORs are inhibitory, these data suggest distinct roles for these neuronal classes in pain modulation. Along with direct excitation, we also found that presynaptic nAChRs enhanced GABAergic release preferentially onto neurons that lacked α7 nAChRs. In addition, presynaptic nAChRs enhanced glutamatergic inputs onto all PAG-RVM projection neuron classes to a similar extent. In behavioral testing, both systemic and intra-vlPAG administration of the α7 nAChR-selective agonist, PHA-543,613, was antinociceptive in the formalin assay. Furthermore, intra-vlPAG α7 antagonist pretreatment blocked PHA-543,613-induced antinociception via either administration method. Systemic administration of submaximal doses of the α7 agonist and morphine produced additive antinociceptive effects. Together, our findings indicate that the vlPAG is a key site of action for α7 nAChR-mediated antinociception.

Basic Hip Arthroscopy: Diagnostic Hip Arthroscopy.

Hip arthroscopy is increasing in popularity for the diagnosis and management of hip preservation. The basics of hip arthroscopy positioning, fluoroscopic assessment, and portal establishment are reviewed in the first 2 parts of this series. This article is the third installment in which we describe a systematic approach to performing a diagnostic hip arthroscopy. A mastery of diagnostic arthroscopy is necessary for surgeons treating hip disorders.

Light Activation of Calcein Inhibits Vesicle Release of Catecholamines.

Calcein, a fluorescent fluid phase marker, has been used to track and visualize cellular processes such as synaptic vesicle fusion. It is also the fluorophore for live cells in the commonly used Live/Dead viability assay. In pilot studies designed to determine fusion pore open size and vesicle movement in secretory cells, imaging analysis revealed that calcein reduced the number of vesicles released from the cells when stimulated with nicotine. Using amperometry to detect individual vesicle release events, we show that when calcein is present in the media, the number of vesicles that fuse with the cellular membrane is reduced when cells are stimulated with either nicotine or high K+. Experimentally, amperometric electrodes are not undergoing fouling in the presence of calcein. We hypothesized that calcein, when activated by light, releases reactive oxygen species that cause a reduction in secreted vesicles. We show that when calcein is protected from light during experimentation, little to no reduction of vesicle secretion occurred. Therefore, photoactivated calcein can cause deleterious results for measurements of cellular processes, likely to be the result of release of reactive oxygen species.

Perioperative Nursing Management of Donor and Recipient Patients Undergoing Face Transplantation.

Individuals with debilitating facial injuries and deformities have achieved significant improvement of aesthetic form and function after undergoing a face transplantation. The involvement of surgical technologists and perioperative nurses in the care of the recipient and donor plays a critical role in the success of these procedures. There are unique challenges that staff members may be presented with when caring for a donor and recipient undergoing a face transplantation, including less comfort with and knowledge of the surgical procedure and instrumentation, an increased amount of equipment and personnel in the OR, donor and recipient admission and discharge care, and increased shift length. At New York University Langone Medical Center, New York, we have developed a comprehensive process to prepare staff members to care for patients undergoing face transplantation.

Demographic and infection characteristics of patients with carbapenem-resistant Enterobacteriaceae in a community hospital: Development of a bedside clinical score for risk assessment.

BACKGROUND: The objective of this study was to identify risk factors associated with the presence of carbapenem-resistant Enterobacteriaceae (CRE) infections to develop a clinical prediction model that can be used at patient bedside to identify subjects likely infected with a CRE pathogen. METHODS: This case-control study included patients aged ≥18 years admitted to Novant Health Forsyth Medical Center between January 1, 2012, and December 31, 2013, with CRE infections (cases) or non-CRE infections (controls). Controls were matched to their corresponding resistant case (3:1) based on pathogen, place of likely acquisition, isolate source, year of admission, and level of care. A risk prediction model was developed using variables independently associated with CRE isolation. Sensitivities and specificities were obtained at various point cutoffs, and a determination of the receiver operator characteristic (ROC) area under the curve (AUC) was performed. RESULTS: A total of 164 subjects were included. Independent risk factors for CRE included recent antibiotic therapy, recent immunosuppression, and Charlson Comorbidity Index score ≥4. Adjusted odds ratios were 13.37 (95% confidence interval [CI], 4.16-61.19), 6.69 (95% CI, 1.85-29.65), and 3.30 (95% CI, 1.34-8.40), respectively. Diagnostic performance of various score cutoffs for the model indicated a score ≥5 correlated with the highest accuracy (79%). The ROC AUC was 0.83. CONCLUSION: The risk prediction model displayed good discrimination and was an excellent predictor of CRE infection.

Epigenetic mechanisms in schizophrenia.

Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have been implicated in a number of complex diseases. Schizophrenia and other major psychiatric and neurodevelopmental disorders are associated with abnormalities in multiple epigenetic mechanisms, resulting in altered gene expression during development and adulthood. Polymorphisms and copy number variants in schizophrenia risk genes contribute to the high heritability of the disease, but environmental factors that lead to epigenetic modifications may either reduce or exacerbate the expression of molecular and behavioral phenotypes associated with schizophrenia and related disorders. In the present paper, we will review the current understanding of molecular dysregulation in schizophrenia, including disruption of the dopamine, NMDA, and GABA signaling pathways, and discuss the role of epigenetic factors underlying disease pathology.

Post-DSAEK optical changes: a comprehensive prospective analysis on the role of ocular wavefront aberrations, haze, and corneal thickness.

PURPOSE: The aim was to assess the visual impact of ocular wavefront aberrations, corneal thickness, and corneal light scatter prospectively after performing a Descemet stripping automated endothelial keratoplasty (DSAEK) in humans. METHODS: Data were obtained prospectively from 20 eyes preoperatively and at 1, 3, 6, and 12 months post-DSAEK. At each visit, the best spectacle-corrected visual acuity and visual acuity with glare (brightness acuity testing) were recorded, and ocular wavefront measurements and corneal optical coherence tomography (OCT) were performed. The magnitude and the sign of individual Zernike terms [higher-order aberrations (HOAs)] were determined. Epithelial, host stromal, donor stromal, and total corneal thicknesses were quantified. The brightness and intensity profiles of OCT images were generated to quantify light scatter in the whole cornea, subepithelial region, anterior and posterior host stroma, interface, and donor stroma. RESULTS: The mean best spectacle-corrected visual acuity and glare disability at low light levels improved from 1 to 12 months post-DSAEK. All corneal thicknesses and ocular lower-order aberrations and HOAs were found to be stable from 1 to 12 months, whereas total corneal, host stromal, and interface brightness intensities decreased significantly over the same period. A repeated measures analysis of variance performed across the follow-up period revealed that the change in scatter, but not the change in the HOAs, could account for the variability occurring in the acuity from 1 to 12 months post-DSAEK. CONCLUSIONS: Although ocular HOAs and scatter are both elevated over normal values post-DSAEK, our results demonstrate that the improvements in visual performance occurring over the first year post-DSAEK are associated with decreasing light scatter. In contrast, there were no significant changes in the ocular HOAs during this time. Because corneal light scatter decreased between 1 and 12 months despite there being stable corneal thicknesses over the same period, we conclude that factors that induced light scatter, other than tissue thickness or swelling (corneal edema), significantly impacted the visual improvements that occurred over time post-DSAEK. A better understanding of the cellular and extracellular matrix changes of the subepithelial region and interface, incurred by the surgical creation of a lamellar host-graft interface, and the subsequent healing of these tissues, is warranted.

Central circadian control of female reproductive function.

Over the past two decades, it has become clear just how much of our physiology is under the control of the suprachiasmatic nucleus (SCN) and the cell-intrinsic molecular clock that ticks with a periodicity of approximately 24 h. The SCN prepares our digestive system for meals, our adrenal axis for the stress of waking up in the morning, and the genes expressed in our muscles when we prepare to exercise. Long before molecular studies of genes such as Clock, Bmal1, and the Per homologs were possible, it was obvious that female reproductive function was under strict circadian control at every level of the hypothalamic-pituitary-gonadal axis, and in the establishment and successful maintenance of pregnancy. This review highlights our current understanding of the role that the SCN plays in regulating female reproductive physiology, with a special emphasis on the advances made possible through the use of circadian mutant mice.

Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.

Mutations that cause intellectual disability (ID) and autism spectrum disorder (ASD) are commonly found in genes that encode for synaptic proteins. However, it remains unclear how mutations that disrupt synapse function impact intellectual ability. In the SYNGAP1 mouse model of ID/ASD, we found that dendritic spine synapses develop prematurely during the early postnatal period. Premature spine maturation dramatically enhanced excitability in the developing hippocampus, which corresponded with the emergence of behavioral abnormalities. Inducing SYNGAP1 mutations after critical developmental windows closed had minimal impact on spine synapse function, whereas repairing these pathogenic mutations in adulthood did not improve behavior and cognition. These data demonstrate that SynGAP protein acts as a critical developmental repressor of neural excitability that promotes the development of life-long cognitive abilities. We propose that the pace of dendritic spine synapse maturation in early life is a critical determinant of normal intellectual development.

Lemierre syndrome causing bilateral cavernous sinus thrombosis.

Lemierre syndrome is an uncommon septic thrombophlebitis of the veins of the head and the neck usually occurring after a severe oropharyngeal infection. Although subsequent septic emboli most commonly affect distant sites, such as the lungs and joints, the authors present a case of Lemierre syndrome causing bilateral cavernous sinus syndrome.

Training children with ADHD to minimize impulsivity in auditory contralateral masking.

OBJECTIVE: Impulsivity and distractibility are among the important symptoms of attention deficit hyperactivity disorder (ADHD). In this study, impulsivity is operationally measured using false-alarm rates in an auditory, contralateral-masking task. Intensive auditory training was attempted to decrease false alarm rates. METHODS: In contralateral masking there is a distracting noise in one ear on every trial and a threshold-level tone in the other ear on half of those trials. Participants indicated whether the tone was present or not and received immediate feedback. The intensity of the masked tone was adaptively varied to track threshold. False alarms are the error of commission, saying that a stimulus is present when it is not. Seven school-aged children with ADHD (ages 10-16) and four adults without ADHD were trained on this task for 900 trials per day over four consecutive days. RESULTS: False alarms from the children with ADHD decreased over the four days of training, beginning at the high level and ending at the low level expected from previous studies. There was no generalization to a different masking task. Results from the four adults were unexpected: soon after the training began they behaved no differently than the children with ADHD. CONCLUSION: Children with ADHD can be trained to become less impulsive in an auditory detection task.