The Impact of Multidisciplinary Weight Management on Body Weight and Body Mass Composition in Women with Breast Cancer Post-Adjuvant Chemotherapy: A Retrospective Chart Review.

INTRODUCTION: Weight gain during chemotherapy for breast cancer is a well-documented adverse effect. The purpose of this study was to investigate how multidisciplinary weight management involving endocrinology, dietitian, and exercise physiology care, in a real-life healthy weight clinic (HWC) would impact body weight and mass composition in breast cancer women post-adjuvant chemotherapy compared to a cohort of non-cancer women who have been matched by age, ethnicity, smoking, and menopausal status. METHODS: Body weight (kg), BMI (kg/m2), skeletal muscle mass (SMM %), fat mass (FM %), and waist circumference (cm) were collected at baseline of the first HWC appointment, 3 months after baseline, and 6 months after baseline. A total of 32 women were included, 11 in the breast cancer cohort and 21 in the control cohort, that matched inclusion and exclusion criteria based on a retrospective chart review from 28 July 2017 to 19 July 2021. RESULTS: By 6 months, the breast cancer women had a mean weight change of -6.99 kg (SD = 3.87, p = 0.003, n = 11) and change in BMI by -2.72 kg/m2 (SD = 1.62, p = 0.004, n = 11). There was a change in SMM of 1.21% (SD = 0.73, p = 0.005, n = 11), a change in FM of -2.76% (SD = 1.33, p = 0.002, n = 11), and a change in waist circumference of -8.13 cm (SD = 4.21, p = 0.031, n = 3). By 6 months in the breast cancer cohort, there was a larger change in body weight in women who did not have MetS (-8.72 kg, SD = 2.41, n = 6) in comparison to women with MetS (-2.65 kg, SD = 3.75 kg, n = 3) (p = 0.045). CONCLUSION: Findings indicate that multidisciplinary weight management has a positive role in early-stage breast cancer survival through improving body weight and mass composition. These results can add to the development of long-term treatment plans for survivors in order to shine a light on ways to reduce risk recurrence and chronic disease mortality.

Evaluation of the in vivo effects of various laser, light, or ultrasound modalities on human skin treated with a collagen and polymethylmethacrylate microsphere dermal filler product.

BACKGROUND: Bellafill® is a soft tissue dermal filler composed of non-resorbable polymethylmethacrylate (PMMA) microspheres, suspended in a water-based carrier gel composed of 3.5% bovine collagen. It has been approved by the FDA for the correction of nasolabial folds and atrophic facial acne scars. Energy-based therapies are used for facial rejuvenation and treatment of acne scarring. However, little has been published about the effects of energy devices on previously placed PMMA. This prospective, in vivo clinical study evaluated the safety and histopathological effects of a number of different laser, light, and ultrasound treatment modalities on PMMA-collagen filler previously injected into human tissue. METHODS: Following a negative reaction to the bovine collagen skin test, the abdomen of one subject (with planned mini-abdominoplasty) was divided into a grid with 32 treatment sections. Seventeen treatment areas received subdermal injections of PMMA-collagen product (0.1-0.2 cc in each area). The subject was assessed for adverse events at each post-treatment office visit. Eighty days post-injection, 30 treatment sections were treated with laser, light, or ultrasound therapy (16 of the 17 PMMA-collagen treated areas, with two of those areas receiving a combination of therapies, and an additional 14 areas receiving laser therapy alone). One PMMA-collagen treated area was not exposed to any energy devices, and one remaining treatment area received no treatment of any kind, representing an internal control. Sixty days following energy device treatment, the tissue was excised in a planned mini-abdominoplasty procedure and sent for histological examination. RESULTS: The subject experienced no adverse events during the study. No histological changes in PMMA microspheres were observed in any treatment area. An expected lymphohistiocytic response was identified in all areas where PMMA microspheres were present. CONCLUSION: Laser, light, and ultrasound treatments can safely be administered following a PMMA-collagen injection. Lasers Surg. Med. 48:811-819, 2016. © 2016 Wiley Periodicals, Inc.

Pilot, Multicenter, Open-Label Evaluation of Safety, Tolerability and Efficacy of a Novel, Topical Multipotent Growth Factor Formulation for the Periorbital Region.

BACKGROUND: This multicenter, open-label pilot study evaluated safety, efficacy and tolerability of a topical formulation containing a multipotent growth factor resignaling complex (MRCx), when applied to infraorbital and lateral canthal skin. METHODS: Thirty-nine female subjects with mean age of 56.8 years who had periorbital lines and wrinkles, uneven skin texture, puffiness, and lack of skin firmness were enrolled, and 38 completed the study. All subjects applied the multipotent growth factor formulation bilaterally to the periorbital area, twice daily for 60 days. Efficacy and treatment-related adverse events were evaluated at Baseline and days 14, 30, and 60. Investigators rated the periorbital areas based on 10-point scales. RESULTS: Subjects' self-reported compliance with treatment was greater than 99% throughout the study. At day 60, all subjects had improvement in infraorbital brightness (≥ 2 points), moistness (≥ 2 points), wrinkles (≥ 1 point), sallowness (≥ 1 point), crepiness (≥ 1 point), smooth texture (≥ 1 point), skin tightness (≥ 1 point), and skin tone (≥ 1 point). Investigator-rated assessments showed ≥ 1-point improvement for lateral canthal wrinkles, dyschromia/mottled pigmentation, skin tone, overall brightness, and moistness. Investigator-rated scoring on the Global Aesthetic Improvement Scale (GAIS) demonstrated that 67.6% of subjects were much improved/improved at day 14, and 63.1% remained improved at day 60. Overall, 76.2% and 79.0% of subjects were very pleased/pleased/mostly pleased with the appearance of their infraorbital and lateral canthal areas at day 60. Adverse events comprised one case of mild canthal erythema, and one case of mild eye irritation, both of which were respectively resolved. CONCLUSIONS: This pilot study demonstrated that the topical multipotent growth factor formulation was safe, effective and well tolerated for periorbital skin rejuvenation.

Afferent loop syndrome 7-years post Roux-en-Y gastrojejunostomy: An often-forgotten pancreatitis cause. A case report.

Afferent loop syndrome is a rare post-operative complication following upper gastrointestinal bypass surgeries, usually occurring within the first two weeks post-operation. This case report, however, outlines afferent loop syndrome almost a decade post-surgery, which was managed conservatively. A 54-year-old woman presented with a few days' history of epigastric pain, vomiting, and constipation. She had undergone a sleeve gastrectomy and was converted to a Roux-en-Y gastrojejunostomy for weight loss 9 and 7 years ago, respectively. Serum lipase was elevated at 1410 IU/L. Computed tomography showed high-grade proximal small bowel obstruction, involving the efferent and afferent loops of the Roux-en-Y gastric bypass. The patient was given intravenous rehydration, electrolyte replacement and had a nasogastric tube inserted. She was discharged on day 5 of admission without significant sequelae. Afferent limb syndrome should be considered in patients with altered upper gastrointestinal anatomy who present with pancreatitis, regardless of the time period post-operatively. Future guidelines should further more outline the factors indicated for surgical versus conservative management.

Massive gastrointestinal bleed due to a primary aortoenteric fistula.

A man in his 60s attended emergency for acute-onset abdominal pain and haematemesis. Requiring resuscitation, a CT abdomen/pelvis revealed a primary aortoenteric fistula actively bleeding into the duodenum. His background included a previous severe Q-fever infection and a heavy smoking history. Despite attempts at resuscitation and an emergent surgical attempt at haemostasis, the patient did not survive the massive gastrointestinal haemorrhage.Even in less severe cases, management of aortoenteric fistulas is tricky. Blood cultures and angiographic imaging are important investigations in guiding surgical approach. The pathology tends to have a significant rate of mortality even at tertiary-level vascular surgical centres.

The Role of Digital Health Technology Interventions in the Prevention of Type 2 Diabetes Mellitus: A Systematic Review.

Objectives: Diabetes in the 21st century presents one of the greatest burdens of disease on the global population. Digitally mediated interventions have become imperative in alleviating this disease epidemic. We aimed to systematically review randomized controlled trials (RCTs) on different health technologies for preventing Type 2 diabetes mellitus, and their efficacy in decreasing diabetes risk-related outcomes in at-risk patients in comparison to standard care. Methods: Five electronic databases were searched between October 2021 and December 2022. Studies including digital health technology interventions used for preventing diabetes development by reducing diabetes risk-related outcomes in at-risk adults (⩾18 years) were identified. Data on glycemic levels, incidence of T2DM, weight, and intervention descriptions were extracted, and the risk of bias (ROB) was assessed. Results: Nine studies met the inclusion criteria and 5 studies (56%) achieved clinically significant outcomes in at least one of the following: decreased weight (22%), glycemic levels (22%), or incidence of T2DM (11%). Two of the 3 (67%) computer-based interventions effectively reduced the HbA1c levels and mean weight of their study population, and 3 of 6 (50%) mobile based interventions (text messages, mobile app, and telehealth) decreased the incidence of T2DM and HbA1c levels. Four studies each had an overall low ROB and one had a high ROB due to attrition. Conclusion: Preliminary evidence identified in our review demonstrated that health technologies for diabetes prevention are effective for improving diabetes risk-related outcomes. Future research into digital technology protocol and studies of longer duration and more diverse populations are needed for clinical feasibility.

Role of Digital technology in Diabetes prevention In the 21st century, diabetes has become a major health challenge globally. To address this, we conducted a systematic review, looking at studies that used digital interventions to prevent Type 2 diabetes mellitus (T2DM) and how effective they are compared to standard care. In this study, we searched electronic databases from October 2021 to December 2022 and identified 9 studies that met our criteria. These studies focused on adults aged 18 and above who were at risk of developing diabetes. We looked at outcomes like glucose concentrations, T2DM incidence, and weight, and assessed the risk of bias in each study. The results showed that more than half of the studies showed significant outcomes. For instance, some interventions led to decreased weight, lower glucose concentrations, or reduced incidence of T2DM. Computer-based interventions and mobile-based interventions (including text messages, mobile apps, and telehealth) were particularly effective in improving these outcomes. In conclusion, our review suggests that digital health technologies can be effective in preventing diabetes and improving related outcomes. However, we note that more research is needed, especially looking at diverse populations and longer study durations, to confirm the clinical feasibility of these digital interventions for diabetes prevention. This is a promising step forward in using technology to tackle the growing diabetes epidemic, offering new ways to support individuals at risk and improve their health outcomes.

A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder.

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation. Enzymatic assessment of variant deleteriousness in vitro revealed protein domain-specific perturbation, complemented by protein structure modeling in silico. We reproduced NADSYN1-dependent CNDD in mice and assessed various maternal NAD precursor supplementation strategies to prevent adverse pregnancy outcomes. While for Nadsyn1+/- mothers, any B3 vitamer was suitable to raise NAD, preventing embryo loss and malformation, Nadsyn1-/- mothers required supplementation with amidated NAD precursors (nicotinamide or nicotinamide mononucleotide) bypassing their metabolic block. The circulatory NAD metabolome in mice and humans before and after NAD precursor supplementation revealed a consistent metabolic signature with utility for patient identification. Our data collectively improve clinical diagnostics of NADSYN1-dependent CNDD, provide guidance for the therapeutic prevention of CNDD, and suggest an ongoing need to maintain NAD levels via amidated NAD precursor supplementation after birth.

Pattern of mental health attendances at a metropolitan university general practice clinic in Sydney before and during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The aim of this study was to describe the pattern of mental health attendances in a university-based general practice clinic during phases of the COVID-19 pandemic. The COVID-19 pandemic has created social and medical disruptions to the Australian community. There is a literature gap pertaining to the ongoing trends that extend beyond the initial 'first wave' of the pandemic in the context of the Australian landscape. METHOD: Retrospective data were obtained from 435 adults attending a community university-based general practice in Sydney, Australia, during four time periods: T1, before the COVID-19 pandemic (1 February - 7 March 2019); T2, during the first COVID-19 lockdown (31 March - 4 May 2020); T3, during the second COVID-19 lockdown (20 August - 23 September 2021); and T4, after the end of the COVID-19 lockdowns (1 February - 7 March 2022). Attendances were identified as mental health Medicare Benefits Schedule codes for face-to-face, televideo and telephone consultations. Patterns of attendances were evaluated using frequency analysis. RESULTS: There was a decline in mental health attendances compared to all attendances at the general practice from T1 (7.5%) to T2 (4.8%). During T4, mental health attendances returned to 7.1% of all consultations at the general practice. Face-to-face attendances decreased by 50% in T2 relative to T1, and this trend was maintained in T3 and T4, whereas the utilisation of telehealth approached that of face-to-face by T4. DISCUSSION: Post-pandemic policies that support the use of telehealth in general practice may help improve mental healthcare delivery and outcomes.

From Microcytosis to Macrodiagnosis.

A 12-year-old Hispanic girl presented with fatigue, lightheadedness, and intermittent headaches. She was depressed and appeared pale to her mother. Her examination was unremarkable except for palpebral conjunctival pallor and was otherwise noncontributory. She had a profound hypoproliferative microcytic anemia with low iron level, low transferrin saturation, and a normal ferritin level. The patient experienced improvement in clinical symptoms following transfusion of packed red blood cells and oral iron therapy. At follow-up 2 months later, she presented with similar symptoms and persistent microcytic anemia with low iron levels. Her ferritin level was increased along with markedly elevated C-reactive protein and erythrocyte sedimentation rate. An oral iron challenge demonstrated lack of absorption, and hepcidin level was also significantly elevated. Thorough gastrointestinal and rheumatologic evaluations were performed to search for a source of inflammation. Key components of the patient's social history supplemented by serology, radiographic, and pathologic findings ultimately cinched an unexpected diagnosis.

(R)-N-Methyl-3-(3'-[F]fluoropropyl)phenoxy)-3-phenylpropanamine (F-MFP3) as a potential PET imaging agent for norepinephrine transporter.

A decline of norepinephrine transporter (NET) level is associated with several psychiatric and neurological disorders. Therefore positron emission tomography (PET) imaging agents are greatly desired to study the NET pathway. We have developed a C-fluoropropyl analog of nisoxetine: (R)-N-methyl-3-(3'-[(18)F]fluoropropyl)phenoxy)-3-phenylpropanamine ((18)F-MFP3) as a new potential PET radiotracer for NET with the advantage of the longer half-life of fluorine-18 (110 min compared with carbon-11 (20 min). Synthesis of (R)-N-methyl-3-(3'-fluoropropyl)phenoxy)-3-phenylpropanamine (MFP3) was achieved in five steps starting from (S)-N-methyl-3-ol-3-phenylpropanamine in approx. 3-5% overall yields. In vitro binding affinity of nisoxetine and MFP3 in rat brain homogenates labeled with (3)H-nisoxetine gave Ki values of 8.02 nM and 23 nM, respectively. For radiosynthesis of (18)F-MFP3, fluorine-18 was incorporated into a tosylate precursor, followed by the deprotection of the N-BOC-protected amine group with a 15% decay corrected yield in 2.5 h. Reverse-phase chromatographic purification provided (18)F-MFP3 in specific activities of >2000 Ci/mmol. Fluorine-18 labeled (18)F-MFP3 has been produced in modest radiochemical yields and in high specific activities. Evaluation of (18)F-MFP3 in animal imaging studies is in progress in order to validate this new fluorine-18 radiotracer for PET imaging of NET.

Retinoic acid can exacerbate T cell intrinsic TLR2 activation to promote tolerance.

The contribution of vitamin A to immune health has been well established. However, recent evidence indicates that its active metabolite, retinoic acid (RA), has the ability to promote both tolerogenic and inflammatory responses. While the outcome of RA-mediated immunity is dependent upon the immunological status of the tissue, the contribution of specific innate signals influencing this response have yet to be delineated. Here, we found that treatment with RA can dampen inflammation during intestinal injury. Importantly, we report a novel and unexpected requirement for TLR2 in RA-mediated suppression. Our data demonstrate that RA treatment enhances TLR2-dependent IL-10 production from T cells and this, in turn, potentiates T regulatory cell (TREG) generation without the need for activation of antigen presenting cells. These data also suggest that combinatorial therapy using RA and TLR2 ligands may be advantageous in the design of therapies to treat autoimmune or inflammatory disease.

Endoscopic approach to the patient with congenital anomalies of the biliary tract.

Congenital biliary tract anomalies typically present with neonatal cholestasis. In children and adults, endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound are used to evaluate and treat choledochal cysts. Contrarily, endoscopy has traditionally played a minor role in the diagnosis of the cholestatic infant. Recent studies support the incorporation of ERCP into the diagnostic algorithm for biliary atresia and neonatal cholestasis. But at present, most pediatric liver centers do not consider its use essential. This article reviews the congenital biliary tract anomalies in which endoscopy has been shown to contribute to the evaluation of the cholestatic infant.

Toll-like receptor signaling and regulation of intestinal immunity.

The intestine is a complex organ that must maintain tolerance to innocuous food antigens and commensal microbiota while being also able to mount inflammatory responses against invading pathogenic microorganisms. The ability to restrain tolerogenic responses while permitting inflammatory responses requires communication between commensal bacteria, intestinal epithelial cells and immune cells. Disruption or improper signaling between any of these factors may lead to uncontrolled inflammation and the development of inflammatory diseases. Toll-like receptors (TLR) recognize conserved molecular motifs of microorganisms and, not surprisingly, are important for maintaining tolerance to commensal microbiota, as well as inducing inflammation against pathogens. Perturbations in individual TLR signaling can lead to a number of different outcomes and illustrate a system of regulation within the intestine in which each TLR plays a largely non-redundant role in mucosal immunity. This review will discuss recent findings on the roles of individual TLRs and intestinal homeostasis.